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研究生:吳聲宇
研究生(外文):Sheng-Yu Wu
論文名稱:台灣地區年輕型高血壓患者之遺傳流行病學研究
論文名稱(外文):Genetic epidemiology study of young-onset hypertension in Taiwan
指導教授:潘文涵潘文涵引用關係范盛娟范盛娟引用關係周玉山周玉山引用關係
指導教授(外文):Wen-Harn PanCathy SJ FannYuh-Shan Jo
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2001
畢業學年度:90
語文別:中文
論文頁數:128
中文關鍵詞:高血壓連鎖
外文關鍵詞:hypertensionlinkage
相關次數:
  • 被引用被引用:5
  • 點閱點閱:978
  • 評分評分:
  • 下載下載:284
  • 收藏至我的研究室書目清單書目收藏:5
高血壓為心臟血管疾病的重要危險因子, 然其受多重因素影響而不易全面了解其形成之原因。多項研究顯示,年輕型高血壓較之老年型高血壓更為重要, 但是其流行病學特徵在國內並無太多之描述, 加上研究顯示高血壓的形成是有其遺傳本質性,且發病年齡愈輕似乎遺傳效應愈強。由於分子遺傳學於近年來的發展突飛猛進, 因此藉由收錄年輕型高血壓個案, 除了對其臨床特徵作一描述外, 另外在藉由收錄其家人, 以分子生物技術來對年輕型高血壓做家族的遺傳研究, 試圖找出可能影響高血壓的基因位置, 以達到早期發現早期控制的目標,才是預防心臟血管疾病的較佳方式。
本研究自台北榮民總醫院心臟血管內科門診中收取82個年輕型高血壓患者, 再由全國營養調查資料選取年齡及性別配對之控制組與高血壓組進行基本資料的比較, 結果發現在男性方面高血壓組的身體質量指數(body mass index;BMI)值(25.1 Kg/m2 vs 22.34 Kg/m2)及三酸甘油脂(triglyceride;TG)值(153.35 mg/dl vs 98.76 mg/dl)均明顯的高於控制組; 而在女性方面高血壓組的三酸甘油脂(triglyceride;TG)值(121.39 mg/dl vs 76.58 mg/dl)及尿酸(uric acid;UA)值(5.74 mg/dl vs 4.78 mg/dl)均明顯的高於控制組, 膽固醇(cholesterol;CHO)值(158.12 mg/dl vs 181.50 mg/dl)卻明顯的小於控制組。以複數迴歸法(multiple logistic regression)分析發現,將男性BMI值作四等分後,最高四分位組較最低四分位組有9.1倍產生高血壓的危險性,女性則有一僅達邊界不甚明顯性(p=0.073)的BMI相對危險性。女性在尿酸最高四分位組,有12.37倍之相對危險性。而在三酸甘油脂部份,則不論男性或女性,均有含量愈高相對危險性愈高的趨勢,且均有明顯的意義。經過身體質量指數的調整後,無論男女高血壓組的三酸甘油脂值依然明顯高於控制組(152.67 mg/dl vs 111.92 mg/dl; 116.88 mg/dl vs 83.92 mg/dl),而女性高血壓組的膽固醇值依然明顯小於控制組(155.46 mg/dl vs 175.17 mg/dl);顯示TG與年輕型高血壓有明顯之相關性。
在家族遺傳的分析中,共收錄了59個家庭;分成兩個階段來作高血壓基因定位工作。第一階段利用affected-sibpairs的連鎖分析方式,對所選取18個高血壓候選基因附近的microsatellite markers進行掃描,結果發現NPPA基因附近的marker D1S1612 (p=0.0162) ﹑AGT基因附近的marker D1S547 (p=0.0263)﹑LPL基因附近的marker D8S1145(p=0.0284)及ACE基因附近的marker D17S2193 (p=0.0256)與高血壓之間有連鎖的現象;另外在ADRB2基因附近的marker D5S1480雖然在affected-sibpairs的分析中沒有明顯的意義,但是在discordant-sibpairs的分析中卻顯示出連鎖現象(p<0.001)。
在第二階段定位工作中,我們將第一階段中顯連鎖現象的五個區域, 再選取更密集的microsatellite markers, 以TDT(Transmittion disequilibrium test)方法作進一步的檢測;結果發現只有在LPL基因及ACE基因附近的markers表現出明顯的傳遞不平衡的現象。
總結本次研究,位於D8S1145-LPL-D8S322及D17S942-ATA108a05-D17S789區域內可能有重要的高血壓基因存在,而LPL基因及ACE基因包含於此區域內。
Hypertension is one of the most important risk factors for cardiovascular diseases. Despite extensive research examining the causes of blood variation, a significant proportion of blood pressure variation is yet to be explained. Many studies indicated that young-onset hypertension is more important than old-onset hypertension for cardiovascular diseases, but there were not to describe for its clinical trait in Taiwan. With the rapid development of molecular genetic, we would use two methods, one is case-control study, and other is genetic approach to studies the young-onset hypertension for its clinical trait and to find the location of the genes, which caused blood pressure increased.
We have recruited 82 patients from a hypertension clinic at Taipei Veterans General Hospital, Taiwan, and 148 normotensive subjects (73 normotensive subjects in another control group that BMI was matched) were recruited from the sample of The 1st Nutrition and Health Surveillance in Taiwan(NAHSIT I) which was research of Institute of Biomedical Sciences,Academia Sinica,Taipei. In our results, mean age of our young hypertension patients was 26.5 years and 30.8 in men and women, respectively. Comparing to the age-, sex-, and residence- matched control, hypertensive group had significantly higher values of blood pressure, BMI, and serum triglyceride. However, the BMI difference was not significant in women. In addition, hypertensive women had significantly higher level of uric acid, but lower level of cholesterol than their normal controls. Multivariate logistic regression showed consistent findings with the above across group comparison. The highest quartile of BMI was significantly associated with a 9.10 fold risk of having hypertension in men. In women, an elevated risk of hypertension was also observed in the highest BMI quartile, but with a smaller odds ratio and a borderline significance level. The highest quartile of serum uric acid was significantly associated with a 12.37-fold risk of having hypertension in women, but not in men. Serum triglyceride level was strongly and significantly associated with risk of hypertension in a dose-response manner in both sexes. On the contrary, serum cholesterol was inversely associated with the status of young hypertension in women. In the comparison between hypertension patients and their age-, sex-, residence-, and BMI- matched controls. TG level was still significantly higher in young-onset group than normotensive group in both males and females. In women, serum cholesterol level was significantly lower in the hypertensives than in the controls. Previously observed phenomenon of uric acid elevation in hypertensive women disappeared. These findings indicate that young onset hypertension may be associated with a cardiovascular disease (CVD) risk factor clustering phenomenon, i.e., elevation of BMI, triglyceride, and uric acid, individually or simultaneously. Nonetheless, serum triglyceride level was associated with young-onset hypertension independent of BMI.
We have recruited 59 nuclear families in genetic analysis, and two stages were used for our gene-mapping stratagem. In the first stage, the affected sib-pairs method revealed positive signals of linkage for markers of the atrial natriuretic peptide gene (NPPA) (D1S1612, p=0.0162), angiotensinogen gene (AGT) (D1S547. P=0.0263), lipoprotein lipase gene (LPL) (D8S1145, p=0.0284), and angiotensin converting enzyme gene (ACE) (D17S2193, p=0.0256). A borderline p-value for a positive signal was also shown for D5S1480 (p=0.0785), a marker for ADRB2. We focus on high resolution mapping of these genes in second stage, and TDT method was used. In our results revealed positive signals among the markers D8S1145-LPL-D8S322 surround LPL gene and D17S942-ATA108a05-D17S789 surround ACE gene.
Comprehensive genotyping with further markers in these region is underway to confirm whether these genes are linked to young-onset hypertension.
本 文 目 錄
1. 中文摘要……………………………………………………….1
2. 英文摘要……………………………………………………….3
3. 第一章: 導論 ……………………………………….………...5
4. 第一節 高血壓的重要性…………………………………….5
5. 第二節 高血壓的特質及其遺傳性………………………….7
6. 第三節 分子生物技術與遺傳統計的運用…………………10
7. 第四節 主要高血壓基因及其在分子學及家族遺傳的研…..
究現況…………….…………………………………17
8. 第五節 研究目的…………………………………………….39
9. 第二章: 研究過程與方法……………………………………..41
10. 第一節 年輕型高血壓患者的收錄…………………….……..41
11. 第二節 病例對照研究………………………………………...43
12. 第三節 年輕型高血壓患者的家族成員收錄………………...44
13. 第四節 DNA樣本的抽取…………………………………….45
14. 第五節 Microsatellite Markers的選取……………………….47
15. 第六節 聚合鋂鏈反應 (PCR)………………………………..49
16. 第七節 定基因型……………………………………………..51
17. 第八節 統計分析……………………………………………..54
18. 第三章 結果: …………………………………………………59
19. 第一節 病例對照分析結果…………………………………..59
20. 第二節 家族遺傳分析結果…………………………………..61
21. 第四章 討論: …………………………………………………64
22. 第一節 病例對照方面………………………………………..64
23. 第二節 家族遺傳分析方面…………………………………..68
24. 第五章 結論…………………………………………………..76
1. Lifton RP. :Genetic determinants of human hypertension. Proc. Natl. Acad. Sci.
92: 8545-8551, 1995.
2. Pan WH, Huang PC. : Final report to Department of Health on Nutrition and
Health Surveillance (NAHSIT), 1993-1996. Aug, 1997.
3. Schneider EL, Guralnik JM. : The aging of America. Impact on health care
costs. JAMA 263: 2335-2340, 1990.
4. Rose GA. :Hypertension in community. In: Bulpitt CJ,ed: Hanbook of
Hypertension. Vol 6. Epidemiology of hypertension. Amsterdam: Elsevir. 1-14,
1985.
5. Pan WH, Nanas S, Dyer A. : The role of weight in the positive association
between age and blood pressure. Am.J.Epidemiol 124:612-623, 1986.
6. Lee SY, Chou HH, Yang IJ, Lin WH, Chen HT. : A community-base study on
risk factors of hypertension in Luh-Guu township. Chinese Medical Journal 44(4) : 235-241, 1989.
7. Tseng WP. : Outcome among untreated hypertension in the general population
in Taiwan. Chinese Medical Sciences Journal 7(3): 130-132, 1992.
8. Perera GA.: Hypertension vascular disease: description and natural history. J
Chron Dis 1: 33-42, 1955.
9. Buck C, Baker P, Bass M, Donner A. : The prognosis of hypertension according
to age at onset. Hypertension 9: 204-208, 1987.
10. Brown JJ, Lever AF, Robertson JIS. : Salt and hypertension. [letter] Lancet
2: 456, 1984.
11. Khaw K-T, Barrett CE.: The association between blood pressure, age, and
dietary sodium and potassium: a population study. Circulation 77:53-61,1988.
12. Bruce NG, Cook DG, Shaper AG, Ratcliffe JG, Thomson AG. : Casual urine
concentrations of sodium and potassium and geographic blood pressure
variations in Great Britain. J Hum Hypertens 6:157-164, 1992.
13. Tai TY, Chuang LM, Chen CJ.: Link between hypertension and diabetes
mellitus: epidemiological study of Chinese adluts in Taiwan. Diabetes Care
14:1013-1020, 1991.
14. He J, Klag MJ, Whelton PK.: Body mass and blood pressure in a lean
Population in southwestern China. Am J Epidemiol 139:380-389, 1994.
15. Phillips A, Shaper AG.: Relative weight and mojor ischaemic heart disease
events in hypertension men. Lancet 1:1005-1008, 1989.
16. Bonaa KH, Thelle DS.: Association between blood pressure and serum lipids
in a population. Circulation 83:1305-1314, 1991.
17. Hall AP.: Correlation among hyperuricemia, hypercholesterolemia, coronary
disease and hypertension. Arthritis Rheum 8:846-852, 1965.
18. Pan WH, Chen YC, Yu SL.: Correlated and predictive models for blood
pressure values in residents of two communities in Taiwan. J Formos Med
Assoc 93:582-591, 1994.
19. Fuh MT, Shieh SM, Wu DA, Chen YD, Reaven GM.: Abnormalities of
Carbohydrate and lipid metabolism in patients with hypertension. Arch Intern
Med 147:1035-1038, 1987.
20. Williams OD Rywik S, Sznajd J.: Poland and US collaborative study on
cardiovascular epidemiology. III. Correlates of systolic and diastolic blood
pressure in men and women aged 35-64years from selected polish rural, polish
urban, and US samples. Am J Epidemiol 130:457-468, 1989.
21. Modan M, Halkin H, Almong S.: Hyperinsulinemia: a link between
hypertension, obesity and glucose intolerance. J Clin Invest 75:809-817,1985.
22. Florey C du V, Uppal S, Lowy C.: Relationship between blood pressure, weight and plasma sugar and serum insulin level in school-children aged 9-12years in Westland, Holland. Br Med J 1:1368-1371, 1976.
23. Breckenridge A.: hypertension and hyperuricemia. Lancet 1:15-18, 1966.
24. Tuomilehto J, Zimmet P, Wolf E.: Plasma uric acid level and its association
with diabetes and some biologic parameters in a biracial population of Fiji.
Am J Epidemiol 127:321-336, 1988.
25. Klatsky AL, Friedman GD, Siegelaub AB.: Alcohol consumption and blood
pressure. N Engl J Med 296:1194-1200, 1977.
26. Dyer AR, Liu K, Walsh M, Kiefe C, Jacobs DR, Bild DE.: Ten-year incidence
of elevated blood pressure and its predictors: The CARDIA study. J Hum
Hypertens 13:13-21, 1999.
27. Ford E, Cooper RS. : Risk factors in for hypertension in a national cohort study. Hypertension 18:598-606, 1991.
28. Sullivan JM.: Salt sensitivity. Definition, conception, methodology, and long-
term issues. Hypertension 17(suppl I):I-61-I-68, 1991.
29. Hunts SC, Hasstedt SJ, Kuida H, Stults BM, Hopkins PN, Williams RR.:
genetic heritability and common environmental components of resting and
stressed blood pressure, lipids and body mass index in Utah pedigrees and
twins. Am J Epidemiol 129:625-638, 1989.
30. Jablon S, Neel JV, Gershowitz H, Atkinson GF.: The NAS:NRC twin panel:
methods of construction of the panel, zygosity diagnosis, and proposed use.
Am J Genet 19:133-161, 1967.
31. Ravogli A, Trazzi S, Villani A, Mutti E, Cuspidi C, Sampieri L, De Ambroggi
L, Parati G, Zanchetti A, Mancia G. : Early 24-hour blood pressure elevation
in normotensive with parental hypertension. Hypertension 16:491-497, 1990.
32. Williams RR, Hunt SC, Hasstedt SJ.: Are there interactions and relations
between genetic and environmental factors predisposing to high blood
pressure? Hypertension 18(suppl I):I-29-I-37, 1991.
33. Ward R. Chapter 6: Familial sggregation and genetic epidemiology of blood
pressure. In : Hypertension, pathophysiology, Diagnosis and Management,
edited by JH Laragh and BM Brenner. Raven Press Ltd, New York 1990.
34. Haldane JBS, Smith CAB.: A new estimate of linkage between the genes for
colour- blindness and hemophilia in man. Ann Eugen 14:10-31, 1947.
35. Morton NE.: Sequential tests for the detection of linkage. Am J Hum Genet 7:
277-318, 1955.
36. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE,
Watkins PC.: A polymorphic DNA marker genetically linked to Huntington’s
disease. Nature 306:234-238, 1983.
37. Botstein D, White RL, Skolnick M, Davis RW.: Construction of a genetic
linkage map in man using restriction fragment length polymorphisms. Am J
Hum Genet 32:314-331, 1980.
38. Weber JL, May PE.: Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388-396,1989.
39. Litt M, Luty JA.: A hypervariable microsatellite revealed by in vitro
Amplification of a dinucleotide repeat within the cardiac muscle actin gene.
Am J Hum Genet 44: 397-401, 1989.
40. Haines JL, Pericak-Vance MA. Approach to gene Mapping in complex human diseases. In Chapter11: Genomic Screening. Edited by Haines JL. New York, 1998.
41. Elliott P.: Observational studies of salt and blood pressure. Hypertension
17(Suppl I): I-3-I-8, 1991.
42. Intersalt Cooperative Research Group. Intersalt: an international study of
electrolyte excretion and blood pressure. Results for 24 hour urinary sodium
and potassium excretion. Br Med J 297:319-328, 1988.
43. Culter JA, Follmann D, Elliott P, Suh I.: An overview of randomized trials of
sodium reduction and blood pressure. Hypertension 17(suppl 1):I-27-I-33,
1991.
44. Weinberger MH, Finberger NS. : Sodium and volume senitivity of blood
pressure. Age and pressure change over time. Hypertension 18:67-71, 1991.
45. Guyton AC.: Physiologic regulation of arterial pressure. Am J Cardial 8:401-
407, 1961.
46. Campese VM, Karubian F, Chervu I, Parise M, Sarkies N, Bigazzi R.: Pressor
reactivity to norepinephrine and angiotensin in salt-sensitivity hypertensive
patient. Hypertension 21:301-307, 1993.
47. Manunta P, Evans G, Hamilton BP, Gann D, Resau J, Hamlyn JM.: A new
syndrome with elevated plasma ouabain and hypertension secondary to an
adrenocortical tumor. (Abstract) J Hypertens 10(suppl 4): S27, 1992.
48. Oikawa S, Imai M, Ueno A, Tanak S, Noguchi T, Nakazato H, Kanagawa K,
Fukuda A, Matsuo H.: Cloning and sequence analysis of cDNA encoding a
precursor foe human atrial natriuretiv polypeptide. Nature 309: 724-726, 1984.
49. John SWM, Krege JH, Oliver PM, Hagaman JR, Hodgin JB, Pang SC, Flynn
TG, Smithies O.: Genetic decreases in atrial natriuretic peptide and salt-
sensitive hypertension. Science 267: 679-681, 1995.
50. Rutledge DR, Sun Y, Ross EA.: Polymorphisms within the atrial natriuretic
peptide gene in essential hypertension. J hypertens 13(9):953-955, 1995.
51. Kato N, Sugiyama T, Morita H, Nabika T, Kurihara H, Yamori Y, Yazaki Y.:
Genetic analysis of the artial natriuretic peptide gene in essential hypertension.
Clinical Science 98(3):251-258, 2000.
52. Missale C, Nash SR, Robison SW, Jaber M, Caron MG.: Dopamine receptors:
from structure to function. Physiol Rev. 78:189-225, 1998.
53. Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy
JL, Gelernter JE, Rozmahel R, Yang Y, Israel Y, Seeman P, O’Dowd BF.:
Human dopamine D1 receptor encoded by an intronless gene on chromosome
5. Nature 347:80-83, 1990.
54. Krushkal J, Xiong M, Ferrell R, Sing CF, Turner ST, Boerwinkle E.: Linkage
and association of adrenergic and dopamine receptor genes in the distal
portion of the long arm of chromosome 5 with systolic blood pressure
variation. Hum Molec Genet 7: 1379-1383, 1998.
55. Sato M, Soma M, Nakayama T, Kanmatause K.: Dopamine D1 receptor gene
polymorphism is association with essential hypertension. Hypertension 36(2):
183-186, 2000.
56. Iwai N, Inagami T.: Isolation of preferentially expressed genes in the kidneys
of hypertension rats. Hypertension 17: 161-169, 1991.
57. Szpirer C, Riviere M, Szpirer J, Levan G, Guo DF, Iwai N, Inagami T.:
Chromosomal assignment of human and rat hypertension candidate genes:
type 1 angiotensin II receptor genes and the SA gene. J Hypertens 11: 919-
925, 1993.
58. Iwai N, Ohmichi N, Hanai K, Nakamura Y, Kinoshita M.: Human SA gene
locus as a candidate locus for essential hypertension. Hypertension 23: 375-
380, 1994.
59. Mark LS, Maxwell MH. : Tigerstedt and the discovery of renin. An historical note. Hypertension 1:384-398, 1979.
60. Peach MJ.: Renin-angiotensin system. Biochemistry and mechamisms of action. Physiol Rev 57: 313-370, 1977.
61. Isa MN, Boyd E, Morrison N, Theriault A, Connor JM, Harrap S, Clauser E.: Regional chromosomal localization of the human angiotensinogen gene to 1q42-43 band. (Abstract) Am J Hum Genet 45:A144, 1989.
62. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, Corvol P.: Molecular basis of human hypertension : role of angiotensinogen. Cell 71: 7-20, 1992.
63. Caulfield M, Lavender P, Farrall M, Munroe P, Lawson M, Turner P, Clark AJL.: Linkage of the angiotensinogen gene to human essential hypertension. New Eng J Med 330: 1629-1633, 1994.
64. Caulfield M, Lavender P, Newell-Price J, Farrall M, Kamdar S, Daniel H, Lawson M, DeFreitas P, Fogarty P, Clark AJL.: Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest 96: 687-692, 1995.
65. Atwood LD, Kammerer CM, Samollow PB.: Linkage of essential hypertension to the angiotensinogen locus in Mexican Americans. Hypertension 30:326-330, 1997.
66. Middleton-Price H, van den Berghe J, Harding A, Scott J, Malcolm S.: Analysis of markers on chromosome 1. (Abstract) Cytogenet Cell Genet 46: 662, 1987.
67. Frossard PM, Lestringant GG, Malloy MJ, Kane JP.: Human renin gene BglI
dimorphism associated with hypertension in two independent population. Clin
Genet 56(6): 428-433, 1999.
68. Chiang FT, Hsu KL, Tseng CD, Lo HM, Chern TH, Tseng YZ.: Association of
the renin gene polymorphism with essential hypertension in a Chinese
population. Clin Genet 51: 370-374, 1997.
69. Jeunemaitre X, Rigat B, Charru A, Houot AM, Soubrier F, Corvol P.: Sib pair
linkage analysis of renin gene haplotypes in human essential hypertension.
Hum Genet 88(3): 301-306, 1992.
70. Naftilan AJ, Williams R, Burt D, Paul M, Pratt R,E, Hobart P, Chirgwin J,
Dzau VJ.: A lack of genetic linkage of renin gene restriction fragment length
Polymorphisms with human hypertension. Hypertension 14: 614-618, 1989.
71. Mullins JJ, Peter J, Ganten D.: Fulminant hypertension in transgenic rats
harbouring the mouse Ren-2 gene. Nature 344: 541-544, 1990.
72. Mattei MG, Hubert C, Alhenc-Gelas F, Roeckel N, Corvol P, Soubrier F.:
Angiotesin-I converting enzyme gene is on chromosome 17. (Abstract)
Cytogenet Cell Genet 51:1041, 1989.
73. Berge KE, Berg K.: No effect of insertion/deletion polymorphism at the ACE
locus on normal blood pressure level or variability. Clin Genet 44: 292-297,
1993.
74. Cambien F, Poirier O, Lecerf L.: Deletion polymorphism in the gene for
angiotensin converting enzyme is a potent risk factor for myocardial
infarction. Nature 359: 641-643, 1992.
75. Yoshida H, Mitarai T, Kawamura T, Kitajima T, Miyazaki Y, Nagasawa R,
Kawaguchi Y, Kubo H, Ichikawa I, Sakai O.: Role of the deletion
polymorphism of the angiotensin converting enzyme gene in the progression
and therapeutic responsiveness of IgA nephropathy. J Clin Invest 96:2162-
2169, 1995.
76. Schunkert H, Hense HW, Holmer SR, Stender M, Perz S, Keil U, Lorell BH,
Riegger GAJ.: Association between a deletion polymorphism of the
angiotensin
Converting enzyme gene and left ventricular hypertrophy. New Eng J Med
330: 1634-1638, 1994.
77. Montgomery HE, Clarkson P, Dollery CM, Prasad K, Losi MA, Hemingway
H, Statters D, Jubb M, Girvain M, Varnava A, World M, Deanfield J, Talmud
P, McEwan, JR, Mckenna WJ, Humphries S.: Association of angiotensin
converting enzyme gene I/D polymorphism with chang in left ventricular mass
in response to physical training. Circulation 96: 741-747, 1997.
78. Julier C, Delepine M, Keavney B, Terwilliger J, Davis S, Weeks DE, Bui T,
Jeunemaitre X, Velho G, Froguel P, Ratcliffe P, Corvol P, Soubrier F, Lathrop
GM.: Genetic susceptibility for human familial essential hypertension in a
region of homology with blood pressure linkage on rat chromosome 10. Hum
Molec Genet 6:2077-2085, 1997.
79. Levy D, DeStefano AL, Larson MG, O’Donnell CJ, Lifton RP, Gavras H,
Cupples LA, Mayers RH.: Evidence for a gene influencing blood pressure on
Chromosome 17. Genome scan linkage results for longitudinal blood pressyre
Phenotypes in subjects from the framingham heart study. Hypertension
36:477-483, 2000.
80. Guo DF, Furuta H, Mizukoshi M, Inagami T.: The genomic organization of
human angiotensin II type 1 receptor. Biochem Biophys Res Commun 200:
313-319, 1994.
81. Ito M, Oliverio MI, Mannon PJ, Best CF, Maeda N, Smithies O, Coffman,
TM.: Regulation of blood pressure by type 1A angiotensinII receptor gene.
Proc Nat Acad Sci 92:3521-3525, 1995.
82. Bonnardeaux A, Davis E, Jeunemaitre X, Fery I, Charru A, Clauser E, Tiret L,
Cambien F, Corvol P, Soubrier F.: Angiotensin II type 1 receptor gene
Polymorphism in human essential hypertension. Hypertension 24: 63-69,
1994.
83. Wang WY, Zee RY, Morris BJ.: Association of angiotensin II type 1 receptor
gene polymorphism with essential hypertension. Clin Genet 51(1): 31-4, 1997.
84. Lerch M, Teuscher AU, Beissner P, Schneider M, Shaw SG, Weidmann P.:
Effects of angiotensin II receptor blockade with losartan on insulin sensitivity,
lipid profile, and endothelin in normotensive offspring of hypertensive
parents.
85. Sica DA.: The important of the sympathetic nervous system and systolic
hypertension in patients with hypertension: benefits in treating patients with
increased cardiovascular risk. Blood Pressure Monitoring 5 suppl 2: S19-S25,
2000.
86. Julius S, Krause L, Schork NJ, et al : Hyperkinetic borderline hypertension in
Tecumseh, Michigan. J of hypertension 1991; 9:77-84.
87. Baetge EE, Behringer RR, Messing A, Brinster RL, Palmiter RD.: Transgenic
mice express the human phenylethanolamine N-methyltransferase gene in
adrenal medulla and retina. Proc Nat Acad Sci 85: 3648-3652, 1988.
88. Saavedra JM, Grobeeker H, Axefrod J. Adreneraline-forming enzyme in
brainstem: elevation in genetic and experimental hypertension. Science 191:
483-484, 1976.
89. Saavedra JM.: Adrenaline level in brain stem nuclei and effects of a PNMT
neurons and experimental hypertension in the rat . Brain Res 166:283-292,
1979.
90. Hokfelt T, Fuxe K, Goldstein M, Johansson O.: Evidence for adrenaline
neurons in the rat brain. Acta Physiol Scand 89:286-288, 1973.
91. Hilbert P, Lindpaintner K, Beckmann JS, Serikawa T, Soubrier F, Dubay C,
Cartwright P, De Gouyon B, Julier C, Takahasi S, Vincent M, Ganten D,
Georges M, Lathrop GM.: Chromosomal mapping of two genetic loci
Association with blood-pressure regulation in hereditary hypertension rats.
Nature 353: 521-529, 1991.
92. Jacob HJ, Lindpaintner K, Lincoln SE, Kusumi K, Bunker RK, Mao YP,
Ganten D, Dzau VJ, Lander ES.: Genetic mapping of a gene causing
hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67: 213-
224, 1991.
93. Dage RCCP, Hsleh, Spedding. : Vasodilation by medroxalol mediated by β2-
adrenergic receptor stimulation. J Cardiovasc pharmacol 5:143-150, 1983.
94. Lannqvist FH, Wahrenberg L, Hellstrom S, Reynisdotlr.: Lipolytic
catecholamine resistance due to decrease β2-adrenoceptor expression in fat
cells. J Clin Invest 90:2175-2186, 1992.
95. Kobilka BK, Dixon RAF, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS,
Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ.: cDNA for the human
beta-2-adrenergic receptor: a protein with multiple membrane apanning
domains and encoded by a gene whose chromosomal location is shared with
that of the receptor for platelet-derived growth factor. Proc Nat Acad Sci
84:46-50.1987.
96. Takami S, Wong ZYH, Stebbing M, Harrap SB.: Linkage analysis of
glucocorticoid and β2-adrenergic receptor genes with blood pressure and body
mass index. Am J Physiol 276: H1379-H1384, 1999.
97. Svetkey LP, Timmons PZ, Emovan O, Anderson NB, Preis L, Chen YT.:
Association of hypertension with β2 and α2c10-adrenergic receptor genotype.
Hypertension 27: 1210-1215, 1996.
98. Kotanko PA, Binder J, Tasker P, DeFreltas S, Kamdar AJ, Clark FK, caulfield
M.: Essential hypertension in African Caribbeans associates with a variant of
the β2-adrenoceptor. Hypertension 30: 773-776,1997.
99. Svetkey LP, Chen YT, McKeown SP, Preis L, Wilson AF.: Preliminary
evidence of linkage of salt sensitivity in black Americans at the β2-adrenergic
receptor locus. Hypertension 29:918-922,1997.
100. Timmermann B, Mo R, Luft FC, Gerdts A, Busjahn P, Omvik GH, Li H,
Schuster TF.: β2 Adrenoceptor genetic variation is associated with genetic
predisposition to essential hypertension: the Bergen Blood Pressure Study.
Kidney Int 53: 1455-1460, 1998.
101. Lomasney JW, Cotecchia S, Lorenz W, Leung WY, Schwinn DA, Yang-Feng
TL, Brownstein M, Lefkowitz RJ, Caron MG.: Molecular cloning and
expression of the cDNA for the alpha-1A-adrenergic receptor : the gene for
which is located on human chromosome 5. J Biol Chem 226: 6365-6369,
1991.
102. Yang-Feng TL, Kobilka BK, Caron MG, Lefkowitz RJ, Francke U.:
chromosomal assignment of genes for an alpha-adrenergic receptor and for
another member of this receptor family coupled to guanine nucleotide
regulatory proteins (Abstract) Cytogenet Cell Genet 46:722-723, 1987.
103. Umemura S, Hirawa N, Iwamoto T, Yamaguchi S, Toya Y, Kobayashi S,
Takasaki I, Yasuda G, Tamura K, Ishii M.: Association analysis of restriction
fragment length polymorphism for alpha2-adrenergic receptor genes un
essential hypertension in Japan. Hypertension 23(1 Suppl): I203-6, 1994.
104. Lockette W, Ghosh S, Farrow S, MacKenzie S, Baker S, Miles P, Schork A,
Cadaret L.: Alpha 2-adrenergic receptor gene polymorphism and hypertension
in blacks. Am J Hypertens 8(4 Pt 1): 390-394, 1995.
105. Svetkey LP, Timmons PZ, Emovon O, Anderson NB, Preis L, Chen YT.:
Association og hypertension with beta2- and alpha2c10- adrenergic receptor
genotype. Hypertension 27(6): 1210-1215, 1996.
106. Wion KL, Kirchgessner TG, Lusis A, Schotz MC, Lawn RM.: Human
lipoprotein lipase complementary DNA sequence. Science 235: 1638-1641,
1987.
107. Fojo SS, Law SW, Brewer HB.: Human apolipoprotein C-II: complete nucleic
acid sequence of preapolipoprotein C-II. Proc Nat Acad Sci 81:6354-6357,
1984.
108. Klannemark M, Suurinkeroinen L, Orho-Melander M, Groop L, Taskinen
MP.: Interaction between the Asn291Ser variant of the LPL gene and insulin
resistance on dyslipidaemia in high risk individuals for type 2 diabetes
mellitus. Diabetic Med 17(8): 599-605, 2000.
109. Beil FU, Fojo SS, Brewer HB, Greten H, Beisiegel U.: Apolioprotein C-II
deficiency syndrom due to apo C-II (Hamburg): clinical and biochemical
features and HphI restricyion enzyme polymorphism. Euro J Clin Invest
22:88-95, 1992.
110. Wu DA, Bu X, Warden CH, Shen DDC, Jeng CY, Sheu WHH, Fuh MMT,
Katsuya T, Dzau VJ, Reaven GM, Lusis AJ, Rotter JI, Chen YDI.:
Quantitative trait locus mapping of human blood pressure to a genetic region
at or near the lipoprotein lipase gene locus on chromosome 8p22. J Clin Invest
97(9):2111-2118, 1996.
111. Hunt SC, Province MA, Atwood LD, Sholinsky P, Lalouel JM, Rao DC,
Williams RR, Leppert MF.: No linkage of the lipoprotein lipase locus to
hypertension in Caucasians. J Hypertens 17:39-43, 1999.
112. Hart LM, Stolk RP, Dekker JM, Nijpels G, Grobbee DE, Heine RJ, Maassen
JA.: Prevalence of variants in candidate gene for type 2 diabetes mellitus in
the Netherlands: the Rotterdam study and the Hoorn study. J Clin Endo &
Meta 84(3): 1002-1006, 1999.
113. Krook A, O’Rahilly S.: Mutation insulin receptors in syndromes of insulin
resistance. Bailliere’s Clin Endocrinol Metab 10(1): 97-122, 1996.
114. Seino S, Seino M, Nishi S, Bell GI.: Structure of the human insulin receptor
gene and characterization of its promoter. Proc Nat Acad Sci 86: 114-
118,1989.
115. Ying LH, Zee RY, Griffiths LR, Morris BJ.: Association of a RFLP for the
insulin receptor gene, but not insulin, with essential hypertension. Biochem &
Biophy Res Communi 181(1): 486-492, 1991.
116. Zee RY, Lou YK, Morris BJ.: Insulin variant in intron 9, but not microsatellite
in intron 2, of the insulin receptor gene is associated with essential
hypertension. J Hypertens- Supplement 12(7):S13-S22, 1994.
117. Munroe PB, Daniel HI, Farrall M, Lawson M, Bouloux PM, Caulfield MJ.:
Absence of genetic linkage between polymorphisms of the insulin receptor
gene and essential hypertension. J Hum Hypertens 9(8): 669-70, 1995.
118. Thomas GN, Tomlinson B, Chan JC, Lee ZS, Cockran CS, Critchley JA.: An
insulin receptor gene polymorphism is associated with diastolic blood pressure
in Chinese subjects with components of the metabolic syndrome. Am J
Hypertens 13(7): 745-52, 2000.
119. Furchgott RF, Zawadzki JV.: The obligatory role of endothelial cell in the
relaxation of arterial smooth muscle by acetylcholin. Nature 288: 373-376,
1980.
120. Palmer RMJ, Ferrige AG, Monacada S.: Nitric oxide release accounts for the
biological activity of endothelium-derived relaxing factor. Nature 327: 524-
526, 1987.
121. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA,
Fishman MC.: Hypertension in mice lacking the gene for endothelial nitric
oxide synthase. Nature 377:239-242, 1995.
122. Forte P, Copland M, Smith LM, Milne E, Sutherland J, Benjamin N.: Basal
nitric oxide synthesis in essential hypertension. Lancet 349:837-842, 1997.
123. Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN,
Lamas S, Michel T.: Structure and chromosomal localization of the human
constitutive endothelial nitric oxide synthase gene. J Biol Chem 268: 17478-
17488, 1993.
124. Shoji M, Tsutaya S, Saito R, Takamatu H, Yasujima M.: Positive association
of endothelial nitric oxide synthase gene polymorphism with hypertension in
northern Japan. Life Science 66(26): 2557-62, 2000.
125. Miyamoto Y, Saito Y, Kajiyama N, Yoshimura M, Shimasaki Y, Nakayama M,
Kamitani S, Harada M, Ishikawa M, Kuwahara K, Ogawa E, Hamanaka I,
Takahashi N, Kaneshige T, Teraoka H, Akamizu T, Azuma N, Yoshimasa Y,
Yoshimasa T, Takaaki , Itoh H, Masuda I, Yasue H, Nakao K.: Endothelial
nitric oxide synthase gene is positively association with essential
hypertension. Hypertension 32(1): 3-8, 1998.
126. Benjafield AV, Morris BJ.: Association analyses of endotheial nitric oxide
synthase gene polymorphisms in essential hypertension. Am J Hypertens
13(9): 994-8, 2000.
127. Nakayama T, Soma M, Takahashi Y, Izumi Y, Kanmatsuse K, Esumi M.:
Association analysis of CA repeat polymorphism of the endothelial nitric
oxide synthase gene with essential hypertension in Japanese. Clin Genet 51(1):
26-30, 1997.
128. Hunt SC, Williams CS, Sharma AM, Inoue I, Williams RR, Lalouel JM.: Lack
of linkage between the endothelial nitric oxide synthase gene and
hypertension. J Hum Hypertens 10(1): 27-30, 1996.
129. Arngrimsson R, Hayward C, Nadaud S, Baldursdottir A, Walker JJ, Liston
WA,
Bjarnadottir RI, Brock DJH, Geirsson RT, Connor JM, Soubrier F.: Evidence
for a familial pregnancy- induced hypertension locus in the eNOS gene region.
Am J Hum Genet 61:354-362, 1997.
130. Siffert W, Rosskopf D, Moritz A, Wieland T, Kaldenberg-Stasch S, Kettler N,
Hartung K, Beckman S, Jackobs KH.: Enhanced G protein activation in
immortalized lymphoblasts from patients with essential hypertension. J Clin
Invest 96: 759-766, 1995.
131. Pietruck F, Moritz A, Montemurro M, Sell A, Busch S, Rosskopf D, Virchow
S, Esche H, Brockmeyer N, Jakobs KH, Siffert W.: Selectively enhanced
cellular signaling by G(i) protein in essential hypertension: G-alpha(i2), G-
alpha(i3), G-beta(2) are not mutated. Circ Res 79: 974-983, 1996.
132. Siffert W, Rosskopf D, Siffert G, Bush S, Moritz A, Erbel R, Sharma AM,
Ritz E, Wichmann HE, Jakobs KH, Horsthemke B.: Association of a human
G-protein beta-3 subunit variant with hypertension. Nature Genet 18:45-48,
1998.
133. Seilhamer JJ, Randall TL, Yamanaka M, Johnson LK.: Pancreatic
phospholipase A(2) : isolation of the human gene and cDNA from porcine
pancreas and human lung. DNA 5:519-527, 1986.
134. Frossard PM, Lestringant GG.: Association between a dimorphic site on
chromosome 12 and clinical diagnosis of hypertension in three independent
population. Clin Genet 48: 284-287, 1995.
135. Bianchi G, Tripodi G, Casari G.: Two point mutation within the adducin gene
are involved in blood pressure variation. Proc Natl Acad Sci USA 91: 3999-
4003, 1994.
136. Tripodi G, Valtorta F, Torielli Lchieregatti E, Salardi S, Trusolino L, Menegon
A, Ferrari P, Marchisio P-C, Bianchi G.: Hypertension associated point
mutation in the adducin α and β subunit affected actin cytoskeleton and ion
transport. J Clin Invest 97: 2815-2822, 1996.
137. Taylor SAM, Snell RG, Bukler A, Ambrose C, Duyao M, Church D, Lin CS,
Altherr M, Bates GP, Groot N, Barnes G, Shaw DJ, Lehrach H, Wasmuth JJ,
Harper PS, Housman DE, MacDonald ME, Gusella JF.: Cloning of the alpha-
adducin gene from the Huntington’s disease candidate region of chromosome
4 by exon amplification. Nature Genet 2: 223-227, 1992.
138. Kato N, Sugiyama T, Nabika T, Morita H, Kurihara H, Yazaki Y, Yamori Y.:
Lack of association between the α-adducin locus and essential hypertension in
the Japanese population. Hypertension 31:730-733, 1998.
139. Casari G, Barlassina C, Cusi D, Zagato L, Muirhead R, Righetti M, Nembri P,
Amar K, Gatti M, Macciardi F, Binelli G, Bianchi G.: Association of the α-
adducin locus with essential hypertension. Hypertension 25:320-326, 1995.
140. Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, Glorioso N,
Lanzani C, Manunta P, Righetti M, Rivera R, Stella P, Troffa C, Zasato L,
Bianchi G.: Polymorphisms of the α-adducin and salt sensitivity in patients
with essential hypertension. Lancet 349: 1353-1357, 1997.
141. Ellisen LW, Haber DA.: Hereditary breast cancer. Annu Rev Med 49: 425-436.
142. Velho G, Froguel P.: Genetic , metabolic and clinical characteristic of
marturity onset diabetes of the young. Eur J Endocrinol 138: 233-239, 1998.
143. Lahiri DK, Nurnberger JI Jr.: A rapid non-enzymatic method for the
preparation of HMA DNA from blood for RFLP studies. Nucleic Acid Res
19(19): 5444, 1991.
144. Lange K.: The affected sib-pair method using identity by state relations. Am J
Hum Genet 39: 148-150, 1986.
145. Spielman RS, McGinins RE, Ewens WJ.: Transmission test for linkage
disequilibrium: The insulin gene region and insulin-dependent diabetes
mellitus (IDDM). Am J Hum Genet 52: 506-516, 1993.
146. Spielman RS, Ewens WJ.: The TDT and other family-baseed test for linkage
disequilibrium and association. Am J Hum Genet 59: 983-989, 1996.
147. Spielman RS, Ewens WJ.: A sibship test for linkage in the presence of
association: the sib transmission/ disequilibrium test. Am J Hum Genet 62:
450-480, 1998.
148. Horvath S, Laird NM.: A discordant-sibship test for disequilibrium and
linkage: no need for parental data. Am J Hum Genet 63: 1886-1897, 1998.
149. Glayton D, Jones H.: Transmission/ disequilibrium test for extened marker
haplotypes. Am J Hum Genet 65: 1161-1169, 1999.
150. Corrocher R, Steinmayr M, Ruzzenente O, Brugnara C, Bertinato L, Mazzi M,
Furri C, Bonfanti F, DeSandre G.: Elevation of red cell sodium-lithium
countertransport in hyperlipidemia. Life Sci 36: 649-655, 1985.
151. Carr SJ, Thomas TH, Laker MF, Wilkinson R.: Elevation sodium-lithium
countertransport: a familial marker of hyperlipidaemia and hypertension? J
Hypertens 8:139-146, 1990.
152. Le Quan Sang KH, Mazeaud M, Astarie C, Duranthon V, Driss F, Devynck
MA.: Plasma lipids and platelet membrane fluidity in essential hypertension.
Thromb Haemost 69: 70-76, 1993.
153. Ishizaki M, Teraoka K, Tsuritani I, Honda R, Ishida M, Yamada Y.:
Erythrocyte Na+/K+- ATPase and membrane and serum lipid profiles: as
related to alcohol, body mass index and blood pressure. Clin Exp Hypertens
16:741-759, 1994.
154. Miller MA, Sagnella GA, Markandu ND, MacGregor GA.: Comparison of
calcium, magnesium-ATPase activity and membrane fluidity in patients with
essential hypertension and in normotensive controls. J Hypertens 12: 929-938,
1994.
155. Mingorne G, Henrihsen FL,Greco AV, Krogh LN, Capristo E, Gastaldelli A,
Castagneto M, Ferrannini E, Gasbarrini G, Beck-Nielsen H.: Triglyceride-
induced diabetes associated with familial lipoprotein lipase deficiency.
Diabetes
48: 1258- 1263, 1999.
156. DeFronzo RA.: The effect of insulin on renal sodium metabolism.
Diabetologia 21: 165-171, 1981.
157. Kaplan NM.: The deadly quartet: upper-body obesity, glucose intolerance,
hypertriglyceridemi, and hypertension. Arch Intern Med 149:1514-1520,
1989.
158. Stamler R, Shipley M, Elliott P, Dyer A, Sans S, Stamler J.: Higher blood
pressure in adults with less education. Some explanations from INTERSALT.
Hypertension 19:237-241, 1991.
159. Patterson SM, Gottdiener JS, Hecht Gabriela ,et al : Effect of acute mental
stress on serum lipids : Mediating effects of plasma volume. Psychosom
Med 55:525-532,1993.
160. Eundberg UM, Fredrikson M, Wallin L, et al : Blood lipids as related to
cardiovascular and neuroendocrine function under different conditions in
healthy males and females. Phmacol Biochem Behav 1989;33:381-386.
161. Goldstein DS :Plasma catecholamines and essentital hypertension. An
analytical review. Hypertension 1983;5:86-99.
162. Julius S, Krause L, Schork NJ, et al : Hyperkinetic borderline hypertension in
Tecumseh, Michigan. J of hypertension 1991; 9:77-84.
163. Cobb S, Rose RM.: Hypertension, peptic ulcer, and diabetes in air traffic
controller. JAMA 224:489-492, 1973.
164. Burant CF, Takeda J, Bell GI, Davidson NO.: Fructose transporter in human
spermatozoa and small intestine is GLUT5. J Biol Chem 267: 14523-14526,
1992.
165. Sambandam N, Lim F, Cam MC, Rodrigues B.: Cardiac heparin-releasable
lipoprotein lipase activity in fructose-hypertensive rats: effect of coronary
vasodilation. J Cardio Pharmacol 30: 110-117, 1985.
166. Miatello RM, Damiani MT, Nolly HL.: Cardiovascular kinin-generating
capability in hypertensive fructose-fed rats. J Hypertens 16: 1273-1277, 1998.
167. Hata A, Namikawa C, Sasaki M, Sato K, Nakamura T, Tamura K, Lalouel
JM.: Angiotensinogen as a risk factor for essential hypertension in Japan. J
Clin Invest 93: 1285-1287, 1994.
168. Niu T, Xu X, Cordell HJ, Rogus J, Zhou Y, Fang Z, Lindpaintner K.: Linkage
analysis of candidate genes and gene-gene interaction in Chinese hypertension
sib pairs. Hypertension 33(6): 1332-1337, 1999.
169. Wang WY, Glenn CL, Zhang W, Benjafield AV, Nyholt DR, Morris BJ.:
Exclusion of angiotensinogen gene in molecular basis of human hypertension:
sibpair linkage and association analyses in Australian anglo-caucasians. Am J
Med Genet 87(1): 53-60, 1999.
170. Ching FT, Hsu KL, Tseng CD, Hsiao WH, Lo HM, Chern TH, Tseng YZ.:
Molecular variant M235T of the angiotenogen gene is associated with
essential hypertension in Taiwanses. J Hypertens 15: 607-611, 1997.
171. Lifton RP, Warnock D, Acton RT, Harman L, Lalouel JM.: High prevalence of
hypertension-associated angiotensinogen variant T235 in African Americans.
(Abstract) Clin Res 260A, 1993.
172. Ehrenborg E, Skogsberg J, Ruotolo G, Large V, Eriksson P, Arner P, Hamsten
A.: The Q/E27 polymophism in the beta2-adrenoceptor gene is associated with
increased body weight and dyslipoproteinaemia involving triglyceride-rich
lipoproteins. J Intern Med 247(6): 651-656, 2000.
173. Yamada K, Ishiyama-Shigemoto S, Ichikawa F, Yuan X, Koyanagi A, Koyama
W, Nonaka K.: Polymorphism in the 5’-leader cistron of the beta2-adrenergic
receptor gene associated with obesity and type 2 diabetes. J Clin Endocrin &
Meta 84(5): 1754-1757, 1999.
174. Walker BRDI, Phillips JP, Noon M, Panarelli R, Andrew HV, Edwards DW,
holton JR, seckl Dj, Webb, Watt.: Increased vasoconstrictor sensitivity to
glucocorticoids in essential hypertension. Hypertension 27: 190-196, 1996.
175. Hurley DMD, Accili CA, Stratakis M, Karl N, Vamva-Kopoulos E, Rorer K,
Constantine SI, Taylor Cchrousos GP.: Point mutation causing a single amino
acid substitution in the hormone binding domain of the glucocorticoid receptor
in familial glucocorticoid resistance. J Clin Invest 87,: 680-686, 1991.
176. Malchoff DM, Brufsky A, Reardon G, McDermott P, Javier EC, Bergh CH,
Rowe D, Malchoff CD.: A mutation of the glucocorticoid receptor in primary
cortisol resistance. J Clin Invest 91: 1918-1925, 1993.
177. Watt GC, Harrap SB, Foy CJ, Holton DW, Edwards HV, Davidson HR,
Connor JM, Lever AF, Fraser R.: Abnormalities of glucocorticoid metabolism
and the renin-angiotensin system: a four corners approach to the identification
of genetic determinants of blood pressure. J Hypertens 10: 473-482, 1992.
178. Cantor RM, Davis RC, Hsueh WA, Raffel LR, Buchanan TA, Saad MF.:
Linkage of systolic blood pressure to the lipoprotein lipase for the pleiotropic
effect of a gene contributing to the metabolic syndrome. (Abstract) Am J Hum
Genet 61:A270, 1997.
179. Wang XL, McCredie RM, Wilcken DE.: Common DNA polymorphisms at the
lipoprotein lipase gene. Association with serverity of coronary artery disease
and diabetes. Circulation 93(7): 1339-1345, 1996.
180. Wuyts B, Delanghe J, De-Buyzere M.: Angiotensin I converting enzyme
insertion/deletion polymorphism: clinical implication. Acta Clinica Belg
52(6): 338-349, 1997.
181. O’Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM,Schaefer
EJ, Myer RH, Levy D. Evidence for association and genetic linkage of the
angiotensin-converting enzyme locus with hypertension and blood pressure in
men but women in the Framingham Heart Study. Circulation 97: 1766-1772,
1998.
182. Fornage M, Amos CI, Kardia S, Sing CF, Turner ST, Boerwinkle EF.:
Variation in the region of the angiotensin converting enzyme gene influences
interindividual differences in blood pressure levels in young white males.
Circulation 97: 1773-1779, 1998.
183. Harrison-Bernard LM, Raij L.: Postmenopausal hypertension. Current
Hypertens Reports. 2(2): 202-207, 2000.
184. Broanihan KB, Senanayake PS, Li P, Ferrario CM.: Bi-directional action of
estrogen on the renin-angiotensin system. Br J Med & Bio Res 32(4): 373-
381, 1999.
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9. 7、王玉女、楊清姿、徐亞瑛:居家照護服務及臺灣的現況。長庚護理,1996;7(3):80-85。
10. 47、林笑:骨關節炎病患生活品質及其相關因素之探討。護理研究,1994;2(4):371-378。
11. 49、邱啟潤、呂淑宜、許玉霞、朱陳宜珍、劉蘭英:居家中風病人之主要照顧者負荷情形及其相關因素之探討。護理雜誌,1988;35(1):69-83。
12. 52、施教裕:老人福利服務使用之相關因素的探討。社會工作學刊,1994;3:61-92。
13. 54、郝溪明:老人長期照護中家庭功能之初探。社區發展季刊,1998;83:265- 273。
14. 62、徐宗福、許國敏:某醫院日間照護室收案病患及家庭狀況之研究。中華公共衛生雜誌,1994;13(3):229-241。
15. 63、徐亞瑛、張媚、楊玉枝、黃久美:都市型及鄉村型社區居家中殘病老人主要照護者的負荷及相關影響因素。護理雜誌,1992;39(3):99-105。