Prognostic effect of insertion/deletion polymorphism of the ace gene on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes.

OBJECTIVE: The insertion/deletion (I/D) polymorphism of the ACE gene has been reported to be associated with diabetic microvascular or macrovascular complications. The aim of the present study was to investigate the prognostic effect of I/D polymorphism on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS: A consecutive cohort of 1,281 Chinese patients with type 2 diabetes were followed for 41.3 +/- 21.6 months. Renal end points were defined as renal death and events (need for dialysis, plasma creatinine >/=500 micromol/l, or doubling of plasma creatinine of baseline value >/=150 micromol/l). Cardiovascular end points were defined as cardiovascular death and events, which included ischemic heart disease, heart failure, cerebrovascular accident, and revascularization requiring hospital admission. The I/D polymorphism of the ACE gene was examined by PCR followed by agarose gel electrophoresis.

RESULTS: The frequencies of ACE gene I/D polymorphisms were in Hardy-Weinberg equilibrium. Patients who developed a renal end point (n = 98) had higher frequencies of DD genotype (19.4 vs. 10.8%, P = 0.018) and D allele (41.3 vs. 31.8%, P = 0.006) compared with subjects who did not (n = 1,183). The cumulative rates of renal end points were 10.0, 19.2, and 24.4% in the II (n = 595), DI (n = 539), and DD genotype carriers (n = 147), respectively (log rank P = 0.004). In multiple Cox regression analysis, the occurrence of renal end points remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype (DD versus II, adjusted hazard ratio 2.80 [95% CI 1.49-5.29]). There was no prognostic effect of I/D polymorphism on cardiovascular end points.

CONCLUSIONS: The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular end points in Chinese patients with type 2 diabetes.