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研究生:黃雅芳
論文名稱:血管收縮素轉化基因之插入/刪除多型性和中國人第2型糖尿病新陳代謝症候群相關性之研究
論文名稱(外文):ACE gene Insertion/Delection polymorphism associated with metabolic syndrome in Chinese type 2 diabetic patient
指導教授:陳昇明陳昇明引用關係李洮俊李洮俊引用關係
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生命科學院碩士在職專班
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:2002
畢業學年度:90
語文別:中文
中文關鍵詞:血管收縮素轉化基因第2型糖尿病新陳代謝症候群
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研究指出血管收縮素轉化基因之插入/刪除(Angiotensin Converting Enzyme Insertion/Deletion,ACE I/D )多型性,和糖尿病、高血壓、心血管疾病及糖尿病腎病變有關,血漿血管收縮素轉化濃度亦被發現和第2型糖尿病病人的三酸甘油脂和總膽固醇有關。
本研究的目的為探討是否血管收縮素轉化基因之插入/刪除多型性和新陳代謝症候群有相關。
共收集711位患有第2型糖尿病病人及750位接受健康檢查之受檢人參與此研究,血管收縮素轉化基因之插入/刪除多型性以PCR方法檢測,新陳代謝症候群之定義是以1998年世界衛生組織所建議之標準。
結果顯示711位患有第2型糖尿病病人中有534 (75.1%) 位符合新陳代謝症候群的標準。於對照族群中新陳代謝症候群之盛行率以血管收縮素轉化基因多型性分組分別為I I 9.4 %,I D 11.5 %,DD 15.4 %,而在第2型糖尿病病人則新陳代謝症候群之盛行率分別為I I 68.6 % ,I D 79.2 % ,DD 86.1 % ,ACE 基因之I/D多型性對第2型糖尿病之病人合併新陳代謝症候群是有意義的相關(P=0.001)。當對照族群和第2型糖尿病病人一起分析時,則新陳代謝症候群盛行率為I I 37.9 %,I D 44.5 %,DD 51.0 %,ACE 基因之I/D多型性和新陳代謝症候群,仍然有有意義的相關 (P=0.003),第2型糖尿病病人有DD基因型者亦發現有較高的血脂異常情形
(II/I D/DD = 43.1 %,53.1 %,65.8 %,P <0.001) 及白蛋白尿情形
(II/I D/DD = 36.0 %,44.6 %,50.6 %,P = 0.018),而且亦有較高的血清三酸甘油脂(II/ID/DD=155±114 mg/dl,170±140 mg/dl,199± 132 mg/dl,P <0.05),另外,對照族群有DD基因型者,亦發現有較高的白蛋白尿或腎病變盛行率(II/ID/DD= 5.7 %,14.0 %,15.4 %
P =0.001),但在對照族群之血脂異常之盛行率則並沒有統計上的差異。當對照組和第2型糖尿病病人一併分析,則血管收縮素轉化基因型於血脂異常及腎性蛋白尿有統計上的相關,分別為血脂異常,(II/ID/DD= 34.7 %,41.3 %,52/2 %,P <0.001),腎性蛋白尿或腎病變(II/ID/DD= 20.3 %,28.9 %,33.1 %,P <0.001),另第2型糖尿病病人有新陳代謝症候群和沒有新陳代謝症候群相比較,發現有較高的尿酸數值(6.4±1.8 mg/dl vs 5.3±1.4 mg/dl,P <0.001)。
在中國人的第2型糖尿病病人,血管收縮素轉化基因之I/D多型性已被發現和新陳代謝症候群有相關,這個發現可以提供遺傳學上的證據來解釋在新陳代謝症候群有遺傳群聚的傾向,且本研究結果支持renin-angiotensin system在第2型糖尿病病人中造成病理生理學的代謝異常有相當重要的角色。
Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes。
The goal of this study was to investigate whether ACE gene I/D polymorphism can be associated with metabolic syndrome.
711patients with type 2 diabetes and 750 control subjects were studied. The ACE I/D polymorphism was determined by polymerase chain reaction. The definition and criteria of metabolic syndrome used in this study matched those proposed in the 1998 WHO classification.
Our result revealed that Five hundred and thirty-four out of 711 patients with type 2 diabetes (75.1 %) fulfilled the criteria for metabolic syndrome. The prevalence of metabolic syndrome in control subjects with II, ID, and DD genotype were 9.4 %, 11.5 %, and 15.4 %, respectively, and in patients with type 2 diabetes were 68.6 %, 79.2 % and 86.1 %, respectively. The ACE I/D polymorphism was significantly associated with the syndrome in patients with type 2 diabetes (p=0.001). When pooling the controls with diabetes patients, the prevalence of metabolic syndrome in whole study group with II, ID, and DD genotype were 37.9 %, 44.5 % and 51.0 %, respectively and ACE I/D polymorphism was still significantly associated with the metabolic syndrome (p=0.003). Diabetic patients with DD genotype were also found to have a higher prevalence of dyslipidemia (II/ID/DD=43.1% / 53.1% / 65.8%, p< 0.001) and albuminuria (II/ID/DD=36.0% /44.6% / 50.6%, p=0.018), and have higher serum triglyceride levels (II, ID, DD= 155 ± 114 mg/dl, 170 ± 140 mg/dl, and 199 ± 132 mg/dl respectively, p<0.05).
Control subjects with DD genotype were also found to have higher prevalence of albuminuria or more advanced nephropathy (II/ID/DD= 5.7% /14.0% /15.4%, p= 0.001), while the prevalence of dyslipidemia was not found to be statistically different in the control group. When pooling the controls with diabetes patients, ACE genotype could still be significantly associated with dyslipidemia (II/ID/DD=34.7%/41.3%/52.2%, p<0.001) and albuminuria or more advanced nephropathy (II/ID/DD=20.3%/28.9%/33.1%, p<0.001). Diabetic patients with metabolic syndrome were found to have higher serum uric acid levels than those without metabolic syndrome (6.4 ± 1.8 mg/dl vs 5.3 ± 1.4 mg/dl, p<0.01).
The ACE I/D polymorphism was found to be associated with metabolic syndrome in Chinese patients with type 2 diabetes. This finding may provide genetic evidence to explain the clustering of metabolic syndrome, and suggests that renin-angiotensin system is involved in the pathophysiology of metabolic derangement in patients with type 2 diabetes.
目錄
口試委員會審定…………………………………………… I
博碩士論文授權書………………………………………… II
誌謝………………………………………………………… III
目錄………………………………………………………… V
表目錄……………………………………………………… VII
圖目錄……………………………………………………… VIII
中文摘要…………………………………………………… 1
英文摘要…………………………………………………… 3
第一章 緒論……………………………………………… 5
第一節 研究動機…………………………………… 5
第二節 研究背景…………………………………… 7
第三節 研究目的…………………………………… 9
第四節 簡介糖尿病………………………………… 11
第五節 名詞介紹…………………………………… 15
第二章 文獻探討………………………………………… 17
第三章 研究設計與研究方法…………………………… 20
第一節 研究族群及收集時間……………………… 20
第二節 研究方法…………………………………… 21
第三節 DNA萃取步驟…………………………….. 33
第四節 聚合連鎖反應…………………………… 36
第五節 統計分析…………………………………… 38
第四章 研究結果………………………………………… 39
第五章 討論……………………………………………… 42
第六章 結論……………………………………………… 48
參考資料 ………………………………………………….. 59
參考資料:
Alberti KG, Zimmet PZ : Definition, diagnosis and classification of diabetes mellitus and its complications. 1. Diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet Med 15: 539-553, 1998
Buchanan TA, Thawani H, Kades W, Modrall JG, Weaver FA, Laurel C, Poppiti R, Xiang A, Hsueh W : Angiotensin II increases glucose utilization during acute hyperinsulinemia via a hemodynamic mechanism. J Clin Invest 92 : 720-726, 1993
Cambien F, Alhenc-Gelas F, Herbeth B, Andre JL, Rakotovao R, Gonzales MF, Allegrini J, Bloch C : Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study. Am J Hum Genet 43 : 774-80,1988
Chiang FT, Lai ZP, Chem TH, Tseng CD, Hsu KL, Lo HM, Tseng YZ: Lack of association of the angiotensin converting enzyme polymorphism with essential hypertension in a Chinese population. Am J Hypertens 10:197-201, 1997
Cooper R, McFarlane-Anderson N, Bennett FI, Wilks R, Puras A, Tewksbury D, Ward R, Forrester T: ACE, angiotensinogen and obesity: a potential pathway leading to hypertension. J Hum Hypertens 11 : 107-111, 1997
DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerotic cardiovascular disease. Diabetes Care 14: 173- 194, 1991
Ding PY, Hu OY, Pool PE, Liao W : Does Chinese ethnicity affect the
pharmacoki- netics and pharmacodynamics of angio- tensin-convening enzyme inhibitors? J Hum Hypertens 14:163-170, 2000
Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 355:253-259, 2000
Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma AM: Co-expression of rennin-angiotensin system genes in human adipose tissue. J Hypertens 17:555- 560, 1999
Engeli S, Negrel R, Sharma AM: Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 35:1270-1277, 2000
Fogarty DG, Maxwell AP, Doherty CC, Hughes AE, Nevin NC: ACE gene typing (Letter). Lancet 343:851, 1994
Groop L: Genetics of the metabolic syndrome. Br J Nutri 83 (Suppl. 1):S39-S84, 2000
Haffner SM, Stem MP, Hazuda HP, et al: Cardiovascular risk factors in confmned prediabetic individuals. Dose the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 263:2893-8,1990
Haffner SM, Valdez RA, Hazuda HP , Mitchell BD, Morales PA, Sterm MP: Prospective analysis of the insulin resistance syndrome (Syndrome X). Diabetes 41:715-722,1992
Hansen BC: The metabolic syndrome X. Ann N Y Acad Sci 18:1-24, 1999
Hegele RA, Brunt JH, Connelly PW: Genetic variation on chromosome 1 associated with variation in body fat distribution in men. Circulation 92:1089-1093,1995
Hennes MM, O''Shaughnessy IM, Kelly TM, LaBelle P, Egan BM, Kissebah AH: Insulin-resistant lipolysis in abdominally obese hypertensive individuals: role of the rennin-angiotensin system. Hypertension 28:120-126, 1996
Hsieh M-C, Lin S-R, Hsieh T-J, Hsu CH, Chen HC, Shin SJ, Tsai JH: Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan. Nephrol Dial Transplant 15:1008-1013, 2000
Isomaa B, Lahti K, Almgren P, Nissen M, Tuomi T, Taskinen M-R, Forsen B, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683-689, 2001
Matsusaka T, Hymes J,Ichikawa I: Angiotensin in progressive renal disease: theory and practice. J Am Soc Nephrol 7:2025- 2043, 1996
Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z: Hyperinsulinemia: a link between hypertension, obesity and glucose intolerance. J Clin Invest 75:809-817, 1985
Morris AD, Petrie JR, Ueda S, Connell JM, Elliott HL, Small M, Donnelly R: Pressor and subpressor doses of angiotensin II increase insulin sensitivity in NIDDM: dissociation of metabolic and blood pressure effects. Diabetes 43:1445-1449, 1994
Mykkanen L, Kuusisto J, Pyorala K, Laakso M: Cardiovascular disease risk factors as predictors of type 2 (non-insulin- dependent) diabetes mellitus in elderly subjects. Diabetologia 36:553-559, 1993
Nagi DK, Foy CA, Mohamed-Ali V, Yudkin JS, Grant PJ, Knowler WC: Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indian. Metabolism 47:622-626, 1998
Navis G, van der Kleij FG, de Zeeuw D, de Jong PE: Angiotensin
-converting enzyme gene I/D polymorphism and renal disease. J Mol Med 77:781-791, 1999
Nicholls MG, Richards AM, Agarwal M: The importance of the renin-angiotensin system in cardiovascular disease. J Hum Hypertens 12:295-299, 1998
Phillips M, Speakman E, Kimura B: Levels of angiotensin and molecular biology of the tissue rennin angiotensin system. Regul Pept 434:1-120, 1993
Pujia A, Gnasso A, Irace C, Dominijanni A, Zingone A, Perrotti N, Colonna A, Mattioli PL: Association between ACE-D/D polymorphism and hypertension in type II diabetic subjects. J Hum Hypertens 8: 687-691,1994
Reaven GM: Banting Lecture 1988: role of insulin resistance in human disease. Diabetes 37:1595-1607, 1988
Riagt B ,Hubert C,Alhenc-Gelas F,et al,An insertion/deletion polymorphism in the angiotensin I converting enzyme gene acconting for half the variancd of serum enzyme levels,J Clin Invest 86:1343,1990
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F: An insertion deletion polymorphism in angiotensin I- converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343-1346, 1990
Rigat B, Hubert C, Corvol P, Soubrier F: PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 25;20:1433,1992
Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P: Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary artery disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 91 : 3662-3665, 1994
Schmidt MI, Watson RL, Duncan BB, Metcalf P, Brancati FL, Sharrett AR, Davis CE, Heiss G: Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population. Metabolism 45:699- 706,1996
Shanmugam V, Sell KW , Saha BK: Mistyping ACE heterozygotes. PCR Methods Appl3:120-121, 1993
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 15:1579-1592,1997
Taskinen MR, Lahdenpera S, Syvanne M: New insights into lipid metabolism in non-insulin-dependent diabetes mellitus. Ann Med 28:335-340, 1996
Tiret L, Kee F, Poirier O, Nicaud V, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Amouyel P: Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction. Lancet 341:991-992, 1993
Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F: Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-convening enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51: 197-205,1992
Umemura S, Nyui N, Tamura K, Hibi K, Yamaguchi S, Nakaamaru M, Ishigami T ,Yabana M, Kihara M, Inoue S, lshii M: Plasma angiotensinogen concentrations in obese patients. Am J Hypertens 10:629- 633,1997
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G: Effects of an angiotensin- converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:145-153,2000
Zimmet P, Alberti KGMM: The Changing face of macrovascu1ar disease in noninsulin dependent diabetes mellitus in different cultures: an epidemic in progress. Lancet; 350 Suppl. 1:S1-4. 1997
Zimmet PZ: Kelly West Lecture 1991: challenges in diabetes epidemiology from West to the rest. Diabetes Care 15: 232-252,1992
行政院衛生署:中華民國衛生統計 行政院衛生署1999。
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