Background and objective: An exonic polymorphism G2350A (rs4343) in angiotensin converting enzyme (protein: ACE; gene: ACE) was shown to exert the most significant influence on plasma ACE levels. We therefore performed a meta-analysis to investigate association of ACE G2350A polymorphism with hypertension.
Methods: Published case-control studies in English were identified. A total of four studies with 1699 cases and 1274 controls were identified. A random-effects model was performed irrespective of the between-study heterogeneity. Study quality was assessed in duplicate.
Results: Compared with 2350G, the ACE 2350A allele conferred a protective effect on hypertension (odds ratio (OR) = 0.81; 95% confidence interval (CI), 0.56—1.18; p = .28). Similarly, comparisons of 2350AA and 2350GA with 2350GG generated a nonsignificant reduced risk, respectively. Under the dominant model, the ACE 2350A allele conferred a reduced hypertension risk and such associations were divergent between Han Chinese and Muslims from the Arab Gulf and Pakistan. Under the recessive model, this protective effect was totally reversed (OR = 1.01; 95% CI, 0.77—1.33; p = .94). Subgroup analyses indicated a significant protective effect of ACE 2350A compared with 2350G among Muslims from the Arab Gulf and Pakistan (OR = 0.55; 95% CI, 0.42—0.71; p < .00001). No publication biases were observed.
Conclusions: Our results demonstrate that the ACE 2350A allele is associated with a significantly reduced hypertension risk among Muslims from the Arab Gulf and Pakistan, yet an elevated risk among Han Chinese.
Niu W., Qi Y., Cen W. et al. Genetic polymorphisms of angiotensinogen and essential hypertension in a Tibetan population. Hypertens Res2007 ; 30: 1129-1137.
2.
Niu WQ, Zhao HY, Zhou L. et al. Interacting effect of genetic variants of angiotensin II type 1 receptor on susceptibility to essential hypertension in Northern Han Chinese . J Hum Hypertens2009; 23: 68-71.
3.
Nakai K.,Itoh C.Miura Y. et al. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation1994; 90: 2199-2202.
4.
Kaski JC, Fernandez-Berges D.Secondary prevention after acute myocardial infarction and coronary revascularisation: focus on angiotensin converting enzyme inhibitors. Cardiovasc Drugs Ther2008; 22: 185-191.
5.
Danser AH, Schalekamp MA, Bax WA et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/ insertion polymorphism. Circulation1995; 92: 1387-1388.
6.
Das M., Pal S., Ghosh A.Angiotensin converting enzyme gene polymorphism (insertion/deletion) and hypertension in adult Asian Indians: a population-based study from Calcutta, India. Hum Biol2008; 80: 303-312.
7.
Ramachandran V., Ismail P., Stanslas J., Shamsudin N., Moin S., Mohd Jas R.Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects. J Renin Angiotensin Aldosterone Syst2008; 9: 208-214.
8.
Bautista LE, Vargas CI, Oróstegui M., Gamarra G.Population-based case-control study of renin-angiotensin system genes polymorphisms and hypertension among Hispanics. Hypertens Res2008; 31: 401-408.
9.
Jiang X., Sheng H., Li J. et al. Association between renin-angiotensin system gene polymorphism and essential hypertension: a community-based study. J Hum Hypertens2009; 23: 176-181.
10.
Mondry A., Loh M., Liu P., Zhu AL, Nagel M.Polymorphisms of the insertion / deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data. BMC Nephrol2005; 6: 1.
11.
Zhu X., Bouzekri N., Southam L. et al. Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure. Am J Hum Genet2001; 68: 1139-1148.
12.
Niu W., Qi Y., Hou S., Zhai X., Zhou W., Qiu C.Haplotypebased association of the renin-angiotensin-aldosterone system genes polymorphisms with essential hypertension among Han Chinese: the Fangshan study. J Hypertens2009; 27: 1384-1391.
13.
Saeed Mahmood M., Saboohi K., Osman Ali S., Bokhari AM, Frossard PMAssociation of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension. J Hum Hypertens2003; 17: 719-723.
14.
Gambaro G., Anglani F., D'Angelo A.Association studies of genetic polymorphisms and complex disease. Lancet2000; 355: 308-311.
15.
Lohmueller KE, Pearce CL, Pike M., Lander ES, Hirschhorn JNMeta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease . Nat Genet2003; 33: 177-182.
16.
Zintzaras E., Lau J.Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol2008; 61: 634-645.
17.
Lau J., Ioannidis JP, Schmid CHQuantitative synthesis in systematic reviews. Ann Intern Med1997; 127: 820-826.
Pan M., Zhu JH, Liu ZH et al. Angiotensin-converting enzyme gene 2350 G/A polymorphism is associated with left ventricular hypertrophy but not essential hypertension. Hypertens Res2007; 30: 31-37.
20.
Alvi FM, Hasnain S. ACE I/D and G2350A polymorphisms in Pakistani hypertensive population of Punjab. Clin Exp Hypertens2009; 31: 471-480.
21.
Hirschhorn JN, Lohmueller K., Byrne E., Hirschhorn K.A comprehensive review of genetic association studies. Genet Med2002; 4: 45-61.
22.
Ju Z., Zhang H., Sun K. et al. Alpha-adducin gene polymorphism is associated with essential hypertension in Chinese: a case-control and family-based study. J Hypertens2003; 21: 1861-1868.
23.
Greene CS, Penrod NM, Williams SM, Moore JHFailure to replicate a genetic association may provide important clues about genetic architecture. PLoS One2009; 4: e5639.
24.
Salanti G., Sanderson S., Higgins JPObstacles and opportunities in meta-analysis of genetic association studies . Genet Med2005; 7: 13-20.
25.
O’Donnell CJ, Lindpaintner K., Larson MG, et al. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation1998; 97: 1766-1772.
