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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

From the Divisions of Clinical Pharmacology (G.N.T., B.T., J.C.N.C., J.A.J.H.C.), Cardiology (J.E.S.), and Endocrinology (J.C.N.C., C.S.C.), Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong, China.

Address correspondence and reprint requests to G. Neil Thomas, PhD, Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Prince of Wales Hospital, Shatin, NT, Hong Kong SAR, China. E-mail: thomas1997{at}cuhk.edu.hk .

OBJECTIVE— In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms—the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT₁R) A1166C polymorphisms—for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome.

RESEARCH DESIGN AND METHODS— The three gene polymorphisms of this crosssectional 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 ² test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance.

RESULTS— No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT₁RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels.

CONCLUSIONS— These findings suggest that these polymorphisms are unlikely to 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 predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects.

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