OP-10：Prognostic Effect of Insertion/Deletion Polymorphism of Angiotensin-Converting Enzyme Gene on Renal and Cardiovascular Clinical Outcomes in Chinese Type 2 Diabetic Patients

Wing Yee So, Ying Wang, Maggie C Y Ng, Peter C Y Tong, Ronald C W Ma, Chun Chung Chow, Clive S Cockram, Juliana C N Chan

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.

Aims/hypothesis. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been reported to be associated with diabetic micro- 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 Type 2 diabetic patients.

Methods. A consecutive cohort of 1,281 Chinese type 2 diabetic patients were followed up for 41.3±21.6 months. Renal endpoint was defined as renal death and events (need for dialysis or plasma creatinine ³500 mmol/l or doubling of plasma creatinine of baseline value ³150 mmol/l). Cardiovascular endpoint was defined as cardiovascular death and events which included ischaemic heart disease, heart failure, cerebrovascular accident and revascularisation requiring hospital admission. The I/D polymorphism of 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 renal endpoint (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 endpoint 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 endpoint remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype [DD vs. II, adjusted hazard ratio 2.80, (95% CI: 1.49, 5.29)]. There was no prognostic effect of I/D polymorphism on cardiovascular endpoint.

Conclusion. The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular endpoint in Type 2 Chinese diabetic patients.