Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia,and diabetes in Hong Kong Chinese - A significant association of the ACE insertion/deletion polymorphism with type 2 diabetes

OBJECTIVE- In Chinese populations, hypertension is common and is a major ri sk factor fur cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidem ia and obesity is termed the metabolic syndrome and is increasing in preval ence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may pl ay a role in the pathogenesis of aspects of the metabolic syndrome. We inve stigated three RAS gene polymorphisms-the ACE insertion/deletion (I/D), ang iotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT(1)R) A1166 C polymorphisms-for a possible role in modulating these disorders in 853 Ch inese subjects with varying components of the metabolic symdrome. RESEARCH DESIGN AND METHODS- The three gene polymorphisms of this cross-sec tional study were detected using polymerase chain reaction-based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes , hypertension, and dyslipidemia using chi (2) test. Differences in levels of the biochemical parameters between the genotypes were determined using a nalysis of variance. RESULTS- No significant relationship was identified between these polymorph isms and blood pressure in this population. Although the AT(1)R A1166C poly morphism was not associated with any aspect of the metabolic syndrome exami ned, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significant ly more frequent in each group comprising subjects with type 2 diabetes/glu cose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels. CONCLUSIONS- These findings suggest that these polymorphisms are unlikely t o be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele-containing genotypes in those groups, but this appeared to result p redominantly from the relationship with type 2 diabetes/GIT in this populat ion of Chinese subjects.