(3.237.97.64) 您好!臺灣時間:2021/03/09 09:37
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:鍾加明
研究生(外文):Chia-Min Chung
論文名稱:血管收縮素轉化酶活性之數量性狀遺傳分析:從連鎖分析和相關研究到對血管收縮素轉化酶活性抑制劑藥物反應之潛在定義
論文名稱(外文):Genetic analysis of quantitative traits for Angiotensin converting enzyme activity: From linkage and association studies to potential implications for response to ACE inhibitors
指導教授:范盛娟范盛娟引用關係潘文涵潘文涵引用關係
指導教授(外文):Cathy SJ FannWen-Harn Pan
學位類別:博士
校院名稱:國立陽明大學
系所名稱:公共衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:117
中文關鍵詞:血管收縮素轉化&血管收縮素轉化&血管收縮素轉化&血管收縮素轉化&血管收縮素轉化&血管收縮素轉化&血管收縮素轉化&
外文關鍵詞:ABOGWASACEHypertensionpharmacogenetic
相關次數:
  • 被引用被引用:0
  • 點閱點閱:241
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
血管收縮素轉化酶在腎素-血管張力素系統中是一個非常重要的酵素,且具有許多的生理功能,因此我們採用兩階段全基因相關研究試圖找尋血管收縮素轉化酶活性之新的數量性狀基因座(QTLs),第一階段針對400個年輕高血壓個案,使用Illumina Infinium II HumanHap 550 SNP chips全基因體掃描平台,進行全基因體掃描的相關性分析。第一階段在ACE基因上有8個SNP跟血管收縮素轉化酶活性有相關,這8個SNP位在ACE基因上,從起始子(promoter)到外顯子(exon24)位置中,-log p值從11.18到20.06,其中以位於外顯子17 上的SNP rs4343的有最高的-log p值,在靠近ACE 基因ID多型性(Intron 16)的位置附近。除了ACE基因以外,另一個-log p超過7的SNP是rs4955828(-log p值=7.59)座落在ABO基因起始子(promoter)上。依照以上的全基因體相關性研究的結果,我們採用-log p值超過7的SNP進入第二階段的證實研究,由於在ACE基因內SNP之間有很強的連鎖不平衡(LD)現象,所以在ACE基因內只挑選一個最顯著的SNP(rs4343),在ABO基因上除了rs495828之外,rs8176746(-log p值=5.59)在ABO基因外顯子7上也被挑選進入第二階段研究。第二階段用額外的623個高血壓研究個案證實了第一階段的研究結果,在第二階段研究中這三個SNP依然和血管收縮素轉化酶活性有相關。rs4343的p值為3.02x10-25,rs495828的p值為3.54x10-8,rs8176746的p值為9.30x10-5。我們更進一步在獨立的年輕型家族研究驗證ABO基因型/血型與ACE活性的相關,同時ABO基因與ACE基因上的SNP所組成的遺傳分數(genetic score)和服用血管收縮素轉化酶抑制劑後的收縮壓反應有關。此外,在年輕型高血壓家族研究之基因細部定位,發現在ACE基因的第二個連鎖不平衡區塊上的標籤單核苷酸(rs1800764)與年輕型高血壓有輕微的相關(P=0.0358),這個結果也在另一個獨立研究再一次被驗證。我們利用單套型的方法及單點SNP與ACE 活性相關(最高的統計p值)結果發現可能影響ACE活性的變異的位置是從外顯子13(rs4316)到3’UTR(rs4366)。本研究結果可讓我們對控制ACE活性的機制更了解,且對血管收縮素轉化酶抑制劑的藥物遺傳學知識有更深的了解。
Because ACE activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage GWAS: (1) a genome-wide association study from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight SNPs of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known Insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (p =3.0x10-25), rs495828 (p =3.5x10-8) and rs8176746 (p =9.3x10-5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/ blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and demonstrated a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE activity–raising alleles. Furthermore, we finemapped ACE gene in order to narrow-down the functional locations. We genotyped 31 SNPs of ACE with 1168 individuals from 305 young-onset hypertension pedigrees. We have discovered a moderate effect variant upstream of ACE promoter for young-onset hypertension and one QTL of ACE activity. The major QTL is in the region between exon13 (rs4316) and 3’UTR (rs4366). These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACE
目錄 I
表目錄 III
圖目錄 IV
中文摘要 V
英文摘要 VII
第一章 前言 1
第二章 文獻探討 4
第一節 高血壓之重要性 4
第二節 高血壓的定義、家族聚集現象及致病機制 5
第三節 高血壓的遺傳研究歷程 8
第四節 使用中介表型找尋高血壓的疾病基因 17
第五節 血管收縮素轉化酶 17
第六節 血管收縮素轉化酶之遺傳研究 20
第三章 材料與方法 36
第一節 血管收縮素轉化酶活性之數量性狀全基因體相關研究 42
第二節 血管收縮素轉化酶活性之基因細部定位研究 48
第四章 研究結果 53
第一節 血管收縮素轉化酶活性之數量性狀全基因體相關研究 53
第二節 血管收縮素轉化酶基因細部定位研究 64
第五章 結論 72
第六章 參考文獻 87

附件一 年輕高血壓家族研究個案同意書 97
附件二 中央研究院多中心高血壓研究個案同意書 99
附件三 103
博士班資格考通過證明
已發表論文


1. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007; 115(5):e69-171.
2. Harrap SB. An appraisal of the genetic approaches to high blood pressure. J Hypertens Suppl 1996; 14(5):S111-115.
3. Hong Y, de Faire U, Heller DA, McClearn GE, Pedersen N. Genetic and environmental influences on blood pressure in elderly twins. Hypertension 1994; 24(6):663-670.
4. Mein CA, Caulfield MJ, Dobson RJ, Munroe PB. Genetics of essential hypertension. Hum Mol Genet 2004; 13 Spec No 1:R169-175.
5. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447(7145):661-678.
6. Gottesman, II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160(4):636-645.
7. Pan WH, Lynn KS, Chen CH, Wu YL, Lin CY, Chang HY. Using endophenotypes for pathway clusters to map complex disease genes. Genet Epidemiol 2006; 30(2):143-154.
8. Castellon R, Hamdi HK. Demystifying the ACE polymorphism: from genetics to biology. Curr Pharm Des 2007; 13(12):1191-1198.
9. Turner AJ, Hooper NM. The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol Sci 2002; 23(4):177-183.
10. Rudnicki M, Mayer G. Significance of genetic polymorphisms of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. Pharmacogenomics 2009; 10(3):463-476.
11. Sayed-Tabatabaei FA, Oostra BA, Isaacs A, van Duijn CM, Witteman JC. ACE polymorphisms. Circ Res 2006; 98(9):1123-1133.
12. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86(4):1343-1346.
13. Zhu X, Bouzekri N, Southam L, Cooper RS, Adeyemo A, McKenzie CA, Luke A, Chen G, Elston RC, Ward R. Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure. Am J Hum Genet 2001; 68(5):1139-1148.
14. Alhenc-Gelas F, Richard J, Courbon D, Warnet JM, Corvol P. Distribution of plasma angiotensin I-converting enzyme levels in healthy men: relationship to environmental and hormonal parameters. J Lab Clin Med 1991; 117(1):33-39.
15. Hinds DA, Stuve LL, Nilsen GB, Halperin E, Eskin E, Ballinger DG, Frazer KA, Cox DR. Whole-genome patterns of common DNA variation in three human populations. Science 2005; 307(5712):1072-1079.
16. Messerli FH, Williams B, Ritz E. Essential hypertension. Lancet 2007; 370(9587):591-603.
17. Pan WH, Chang HY, Yeh WT, Hsiao SY, Hung YT. Prevalence, awareness, treatment and control of hypertension in Taiwan: results of Nutrition and Health Survey in Taiwan (NAHSIT) 1993-1996. J Hum Hypertens 2001; 15(11):793-798.
18. Roman GC. Cerebral congestion. A vanished disease. Arch Neurol 1987; 44(4):444-448.
19. Staessen JA, Wang J, Bianchi G, Birkenhager WH. Essential hypertension. Lancet 2003; 361(9369):1629-1641.
20. Buck C, Baker P, Bass M, Donner A. The prognosis of hypertension according to age at onset. Hypertension 1987; 9(2):204-208.
21. Cowley AW, Jr. Long-term control of arterial blood pressure. Physiol Rev 1992; 72(1):231-300.
22. Schneider EL, Guralnik JM. The aging of America. Impact on health care costs. JAMA 1990; 263(17):2335-2340.
23. Brown JJ, Lever AF, Robertson JI, Semple PF, Bing RF, Heagerty AM, Swales JD, Thurston H, Ledingham JG, Laragh JH, et al. Salt and hypertension. Lancet 1984; 2(8400):456.
24. Khaw KT, Barrett-Connor E. The association between blood pressure, age, and dietary sodium and potassium: a population study. Circulation 1988; 77(1):53-61.
25. 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 1992; 6(2):157-164.
26. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006; 113(6):898-918.
27. Aneja A, El-Atat F, McFarlane SI, Sowers JR. Hypertension and obesity. Recent Prog Horm Res 2004; 59:169-205.
28. Lam TK, Carpentier A, Lewis GF, van de Werve G, Fantus IG, Giacca A. Mechanisms of the free fatty acid-induced increase in hepatic glucose production. Am J Physiol Endocrinol Metab 2003; 284(5):E863-873.
29. Bloomgarden ZT. Obesity, hypertension, and insulin resistance. Diabetes Care 2002; 25(11):2088-2097.
30. Semenkovich CF. Insulin resistance and atherosclerosis. J Clin Invest 2006; 116(7):1813-1822.
31. Park S, Shim J, Kim JB, Ko YG, Choi D, Ha JW, Rim SJ, Jang Y, Chung N. Insulin resistance is associated with hypertensive response to exercise in non-diabetic hypertensive patients. Diabetes Res Clin Pract 2006; 73(1):65-69.
32. Avramoglu RK, Basciano H, Adeli K. Lipid and lipoprotein dysregulation in insulin resistant states. Clin Chim Acta 2006; 368(1-2):1-19.
33. Kontush A, Chapman MJ. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 2006; 58(3):342-374.
34. 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 1980; 32(3):314-331.
35. Weber JL, May PE. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 1989; 44(3):388-396.
36. A haplotype map of the human genome. Nature 2005; 437(7063):1299-1320.
37. Cowley AW, Jr. The genetic dissection of essential hypertension. Nat Rev Genet 2006; 7(11):829-840.
38. Agarwal A, Williams GH, Fisher ND. Genetics of human hypertension. Trends Endocrinol Metab 2005; 16(3):127-133.
39. Ruppert V, Maisch B. Genetics of human hypertension. Herz 2003; 28(8):655-662.
40. Tikhonoff V, Kuznetsova T, Stolarz K, Bianchi G, Casiglia E, Kawecka-Jaszcz K, Nikitin Y, Tizzone L, Wang JG, Staessen JA. beta-Adducin polymorphisms, blood pressure, and sodium excretion in three European populations. Am J Hypertens 2003; 16(10):840-846.
41. 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 1989; 44(3):397-401.
42. Hodge SE, Elston RC. Lods, wrods, and mods: the interpretation of lod scores calculated under different models. Genet Epidemiol 1994; 11(4):329-342.
43. Collins A, Morton NE. Nonparametric tests for linkage with dependent sib pairs. Hum Hered 1995; 45(6):311-318.
44. Abecasis GR, Cardon LR, Cookson WO, Sham PC, Cherny SS. Association analysis in a variance components framework. Genet Epidemiol 2001; 21 Suppl 1:S341-346.
45. Mayeux R. Mapping the new frontier: complex genetic disorders. J Clin Invest 2005; 115(6):1404-1407.
46. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science 1996; 273(5281):1516-1517.
47. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, Debette S, Lumley T, Folsom AR, van den Herik EG, Bos MJ, Beiser A, Cushman M, Launer LJ, Shahar E, Struchalin M, Du Y, Glazer NL, Rosamond WD, Rivadeneira F, Kelly-Hayes M, Lopez OL, Coresh J, Hofman A, DeCarli C, Heckbert SR, Koudstaal PJ, Yang Q, Smith NL, Kase CS, Rice K, Haritunians T, Roks G, de Kort PL, Taylor KD, de Lau LM, Oostra BA, Uitterlinden AG, Rotter JI, Boerwinkle E, Psaty BM, Mosley TH, van Duijn CM, Breteler MM, Longstreth WT, Jr., Wolf PA. Genomewide association studies of stroke. N Engl J Med 2009; 360(17):1718-1728.
48. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H. Genomewide association analysis of coronary artery disease. N Engl J Med 2007; 357(5):443-453.
49. Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw KT, Nilsson P, van der Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, Kuusisto J, Burton PR, Hadley D, McArdle WL, Brown M, Dominiczak A, Newhouse SJ, Samani NJ, Webster J, Zeggini E, Beckmann JS, Bergmann S, Lim N, Song K, Vollenweider P, Waeber G, Waterworth DM, Yuan X, Groop L, Orho-Melander M, Allione A, Di Gregorio A, Guarrera S, Panico S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, Sandhu MS, Luben RN, Crawford GJ, Jousilahti P, Perola M, Boehnke M, Bonnycastle LL, Collins FS, Jackson AU, Mohlke KL, Stringham HM, Valle TT, Willer CJ, Bergman RN, Morken MA, Doring A, Gieger C, Illig T, Meitinger T, Org E, Pfeufer A, Wichmann HE, Kathiresan S, Marrugat J, O'Donnell CJ, Schwartz SM, Siscovick DS, Subirana I, Freimer NB, Hartikainen AL, McCarthy MI, O'Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder H, van Gilst WH, Clarke R, Goel A, Hamsten A, Peden JF, Seedorf U, Syvanen AC, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Dorr M, Ernst F, Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Volker U, Galan P, Gut IG, Hercberg S, Lathrop GM, Zelenika D, Deloukas P, Soranzo N, Williams FM, Zhai G, Salomaa V, Laakso M, Elosua R, Forouhi NG, Volzke H, Uiterwaal CS, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bingham SA, Kooner JS, Connell JM, Bandinelli S, Ferrucci L, Watkins H, Spector TD, Tuomilehto J, Altshuler D, Strachan DP, Laan M, Meneton P, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RJ, Elliott P, Abecasis GR, Caulfield M, Munroe PB. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 2009.
50. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko Y, Lumley T, Kottgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo X, Arking DE, Mitchell GF, Mattace-Raso FU, Smith AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJ, Bis J, Harris TB, Ganesh SK, O'Donnell CJ, Hofman A, Rotter JI, Coresh J, Benjamin EJ, Uitterlinden AG, Heiss G, Fox CS, Witteman JC, Boerwinkle E, Wang TJ, Gudnason V, Larson MG, Chakravarti A, Psaty BM, van Duijn CM. Genome-wide association study of blood pressure and hypertension. Nat Genet 2009.
51. Kammerer CM, Gouin N, Samollow PB, VandeBerg JF, Hixson JE, Cole SA, MacCluer JW, Atwood LD. Two quantitative trait loci affect ACE activities in Mexican-Americans. Hypertension 2004; 43(2):466-470.
52. Wang RY, Chung CM, Fann CS, Yang HC, Chen JW, Jong YS, Jou YS, Lo HM, Ho FM, Kang CS, Chen CC, Chang HC, Shyue SK, Pan WH. Genome-wide scan for quantitative ACE activity in Taiwan young-onset hypertension study. Hum Hered 2008; 65(2):85-90.
53. Hagaman JR, Moyer JS, Bachman ES, Sibony M, Magyar PL, Welch JE, Smithies O, Krege JH, O'Brien DA. Angiotensin-converting enzyme and male fertility. Proc Natl Acad Sci U S A 1998; 95(5):2552-2557.
54. Jeunemaitre X, Lifton RP, Hunt SC, Williams RR, Lalouel JM. Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nat Genet 1992; 1(1):72-75.
55. Wang B, Jin F, Yang Z, Lu Z, Kan R, Li S, Zheng C, Wang L. The insertion polymorphism in angiotensin-converting enzyme gene associated with the APOE epsilon 4 allele increases the risk of late-onset Alzheimer disease. J Mol Neurosci 2006; 30(3):267-271.
56. Danilov S, Savoie F, Lenoir B, Jeunemaitre X, Azizi M, Tarnow L, Alhenc-Gelas F. Development of enzyme-linked immunoassays for human angiotensin I converting enzyme suitable for large-scale studies. J Hypertens 1996; 14(6):719-727.
57. Agachan B, Isbir T, Yilmaz H, Akoglu E. Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. Exp Mol Med 2003; 35(6):545-549.
58. Kario K, Hoshide S, Umeda Y, Sato Y, Ikeda U, Nishiuma S, Matsuo M, Shimada K. Angiotensinogen and angiotensin-converting enzyme genotypes, and day and night blood pressures in elderly Japanese hypertensives. Hypertens Res 1999; 22(2):95-103.
59. Giner V, Poch E, Bragulat E, Oriola J, Gonzalez D, Coca A, De La Sierra A. Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension. Hypertension 2000; 35(1 Pt 2):512-517.
60. Staessen JA, Wang JG, Ginocchio G, Petrov V, Saavedra AP, Soubrier F, Vlietinck R, Fagard R. The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J Hypertens 1997; 15(12 Pt 2):1579-1592.
61. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000; 20(2):484-492.
62. Arbustini E, Grasso M, Fasani R, Klersy C, Diegoli M, Porcu E, Banchieri N, Fortina P, Danesino C, Specchia G. Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction. Br Heart J 1995; 74(6):584-591.
63. Sayed-Tabatabaei FA, Houwing-Duistermaat JJ, van Duijn CM, Witteman JC. Angiotensin-converting enzyme gene polymorphism and carotid artery wall thickness: a meta-analysis. Stroke 2003; 34(7):1634-1639.
64. Keavney B, McKenzie C, Parish S, Palmer A, Clark S, Youngman L, Delepine M, Lathrop M, Peto R, Collins R. Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators. Lancet 2000; 355(9202):434-442.
65. Sharma P. Meta-analysis of the ACE gene in ischaemic stroke. J Neurol Neurosurg Psychiatry 1998; 64(2):227-230.
66. Maeda Y, Ikeda U, Ebata H, Hojo Y, Seino Y, Hayashi Y, Kuroki S, Shimada K. Angiotensin-converting enzyme gene polymorphism in hypertensive individuals with parental history of stroke. Stroke 1996; 27(9):1521-1523.
67. Zee RY, Ridker PM, Stampfer MJ, Hennekens CH, Lindpaintner K. Prospective evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of stroke. Circulation 1999; 99(3):340-343.
68. Ng DP, Tai BC, Koh D, Tan KW, Chia KS. Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects. Diabetologia 2005; 48(5):1008-1016.
69. Boright AP, Paterson AD, Mirea L, Bull SB, Mowjoodi A, Scherer SW, Zinman B. Genetic variation at the ACE gene is associated with persistent microalbuminuria and severe nephropathy in type 1 diabetes: the DCCT/EDIC Genetics Study. Diabetes 2005; 54(4):1238-1244.
70. Wang Y, Ng MC, So WY, Tong PC, Ma RC, Chow CC, Cockram CS, Chan JC. Prognostic effect of insertion/deletion polymorphism of the ace gene on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes. Diabetes Care 2005; 28(2):348-354.
71. Montgomery HE, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Thomas EL, Brynes AE, Saeed N, Barnard M, Bell JD, Prasad K, Rayson M, Talmud PJ, Humphries SE. Human gene for physical performance. Nature 1998; 393(6682):221-222.
72. Kehoe PG, Russ C, McIlory S, Williams H, Holmans P, Holmes C, Liolitsa D, Vahidassr D, Powell J, McGleenon B, Liddell M, Plomin R, Dynan K, Williams N, Neal J, Cairns NJ, Wilcock G, Passmore P, Lovestone S, Williams J, Owen MJ. Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat Genet 1999; 21(1):71-72.
73. Spruth E, Zurbrugg HR, Warnecke C, Erdmann J, Pregla R, Pfautsch P, Hetzer R, Fleck E, Regitz-Zagrosek V. Expression of ACE mRNA in the human atrial myocardium is not dependent on left ventricular function, ACE inhibitor therapy, or the ACE I/D genotype. J Mol Med 1999; 77(11):804-810.
74. Bouzekri N, Zhu X, Jiang Y, McKenzie CA, Luke A, Forrester T, Adeyemo A, Kan D, Farrall M, Anderson S, Cooper RS, Ward R. Angiotensin I-converting enzyme polymorphisms, ACE level and blood pressure among Nigerians, Jamaicans and African-Americans. Eur J Hum Genet 2004; 12(6):460-468.
75. Cox R, Bouzekri N, Martin S, Southam L, Hugill A, Golamaully M, Cooper R, Adeyemo A, Soubrier F, Ward R, Lathrop GM, Matsuda F, Farrall M. Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides. Hum Mol Genet 2002; 11(23):2969-2977.
76. Keavney B, McKenzie CA, Connell JM, Julier C, Ratcliffe PJ, Sobel E, Lathrop M, Farrall M. Measured haplotype analysis of the angiotensin-I converting enzyme gene. Hum Mol Genet 1998; 7(11):1745-1751.
77. McKenzie CA, Abecasis GR, Keavney B, Forrester T, Ratcliffe PJ, Julier C, Connell JM, Bennett F, McFarlane-Anderson N, Lathrop GM, Cardon LR. Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE). Hum Mol Genet 2001; 10(10):1077-1084.
78. Zhu X, McKenzie CA, Forrester T, Nickerson DA, Broeckel U, Schunkert H, Doering A, Jacob HJ, Cooper RS, Rieder MJ. Localization of a small genomic region associated with elevated ACE. Am J Hum Genet 2000; 67(5):1144-1153.
79. Soubrier F, Martin S, Alonso A, Visvikis S, Tiret L, Matsuda F, Lathrop GM, Farrall M. High-resolution genetic mapping of the ACE-linked QTL influencing circulating ACE activity. Eur J Hum Genet 2002; 10(9):553-561.
80. Johnson AD, Gong Y, Wang D, Langaee TY, Shin J, Cooper-Dehoff RM, Schork NJ, Binkley P, Pepine CJ, Johnson JA, Sadee W. Promoter polymorphisms in ACE (angiotensin I-converting enzyme) associated with clinical outcomes in hypertension. Clin Pharmacol Ther 2009; 85(1):36-44.
81. Testut P, Soubrier F, Corvol P, Hubert C. Functional analysis of the human somatic angiotensin I-converting enzyme gene promoter. Biochem J 1993; 293 ( Pt 3):843-848.
82. Blumenfeld OO, Patnaik SK. Allelic genes of blood group antigens: a source of human mutations and cSNPs documented in the Blood Group Antigen Gene Mutation Database. Hum Mutat 2004; 23(1):8-16.
83. 王瑞筠. 「血管收縮素轉化酶活性」連續性狀之基因座搜尋及其結構基因之細部定位; 2007.
84. Buetow KH, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J, Little DP, Strausberg R, Koester H, Cantor CR, Braun A. High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci U S A 2001; 98(2):581-584.
85. Ross P, Hall L, Haff LA. Quantitative approach to single-nucleotide polymorphism analysis using MALDI-TOF mass spectrometry. Biotechniques 2000; 29(3):620-626, 628-629.
86. Kasahara Y, Ashihara Y. Colorimetry of angiotensin-I converting enzyme activity in serum. Clin Chem 1981; 27(11):1922-1925.
87. Etzel CJ, Shete S, Beasley TM, Fernandez JR, Allison DB, Amos CI. Effect of Box-Cox transformation on power of Haseman-Elston and maximum-likelihood variance components tests to detect quantitative trait Loci. Hum Hered 2003; 55(2-3):108-116.
88. Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986; 42(1):121-130.
89. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21(2):263-265.
90. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D. The structure of haplotype blocks in the human genome. Science 2002; 296(5576):2225-2229.
91. Cidl K, Strelcova L, Znojil V, Vachi J. Angiotensin I-converting enzyme (ACE) polymorphism and ABO blood groups as factors codetermining plasma ACE activity. Exp Hematol 1996; 24(7):790-794.
92. Takasaki S, Yamashita K, Kobata A. The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. J Biol Chem 1978; 253(17):6086-6091.
93. Dabelsteen E, Gao S. ABO blood-group antigens in oral cancer. J Dent Res 2005; 84(1):21-28.
94. Podbielska M, Krotkiewski H. [ABO blood-group system: past and present]. Postepy Hig Med Dosw 2002; 56(4):439-460.
95. Borecki IB, Elston RC, Rosenbaum PA, Srinivasan SR, Berenson GS. ABO associations with blood pressure, serum lipids and lipoproteins, and anthropometric measures. Hum Hered 1985; 35(3):161-170.
96. Bezemer ID, Rosendaal FR. Predictive genetic variants for venous thrombosis: what's new? Semin Hematol 2007; 44(2):85-92.
97. Wu O, Bayoumi N, Vickers MA, Clark P. ABO(H) blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost 2008; 6(1):62-69.
98. Jenkins PV, O'Donnell JS. ABO blood group determines plasma von Willebrand factor levels: a biologic function after all? Transfusion 2006; 46(10):1836-1844.
99. Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. II. Results of long-term therapy. Veterans Administration Cooperative Study Group on Antihypertensive Agents. JAMA 1982; 248(16):2004-2011.
100. Arnett DK, Davis BR, Ford CE, Boerwinkle E, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation 2005; 111(25):3374-3383.
101. Belz GG, Breithaupt K, Erb K. Review of studies on the clinical pharmacodynamics of cilazapril. J Cardiovasc Pharmacol 1994; 24 Suppl 2:S14-19.
102. Lang RM, DiBianco R, Broderick GT, Gottlieb SS, Kostis J, Lyle PA, Makris L, Rajfer SI, Rucinska EJ. First-dose effects of enalapril 2.5 mg and captopril 6.25 mg in patients with heart failure: a double-blind, randomized, multicenter study. The Enalapril-Captopril Investigators. Am Heart J 1994; 128(3):551-556.
103. Ehret GB, Morrison AC, O'Connor AA, Grove ML, Baird L, Schwander K, Weder A, Cooper RS, Rao DC, Hunt SC, Boerwinkle E, Chakravarti A. Replication of the Wellcome Trust genome-wide association study of essential hypertension: the Family Blood Pressure Program. Eur J Hum Genet 2008; 16(12):1507-1511.
104. Hong KW, Jin HS, Cho YS, Lee JY, Lee JE, Cho NH, Shin C, Lee SH, Park HK, Oh B. Replication of the Wellcome Trust genome-wide association study on essential hypertension in a Korean population. Hypertens Res 2009; 32(7):570-574.
105. Barley J, Blackwood A, Miller M, Markandu ND, Carter ND, Jeffery S, Cappuccio FP, MacGregor GA, Sagnella GA. Angiotensin converting enzyme gene I/D polymorphism, blood pressure and the renin-angiotensin system in Caucasian and Afro-Caribbean peoples. J Hum Hypertens 1996; 10(1):31-35.
106. Liu X, Fernandez M, Wouters MA, Heyberger S, Husain A. Arg(1098) is critical for the chloride dependence of human angiotensin I-converting enzyme C-domain catalytic activity. J Biol Chem 2001; 276(36):33518-33525.
107. Corvol P WT, Soubrier F. Peptidyl-dipeptidase A/angiotensin 1-converting enzyme, in: Barrett AJ, Rawlings ND, Woessner JF (Eds.), in Handbook of Proteolytic Enzymes. San Diego: Academic Press Inc; 1998.
108. Sethi AA, Nordestgaard BG, Tybjaerg-Hansen A. Angiotensinogen gene polymorphism, plasma angiotensinogen, and risk of hypertension and ischemic heart disease: a meta-analysis. Arterioscler Thromb Vasc Biol 2003; 23(7):1269-1275.
109. Niu T, Chen X, Xu X. Angiotensin converting enzyme gene insertion/deletion polymorphism and cardiovascular disease: therapeutic implications. Drugs 2002; 62(7):977-993.
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔