Prognostic Effect of Insertion/Deletion Polymorphism of the ACE Gene on Renal and Cardiovascular Clinical Outcomes in Chinese Patients With Type 2 Diabetes
- Ying Wang, PHD,
- Maggie C.Y. Ng, BSC, PHD,
- Wing Yee So, MBCHB, MRCP,
- Peter C.Y. Tong, PHD, FRCP,
- Ronald C.W. Ma, MBBCHIR, MRCP,
- Chun Chung Chow, MBBS, FRCP,
- Clive S. Cockram, MD, FRCP and
- Juliana C.N. Chan, MD, FRCP
- From the Department of Medicine & Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
- Address correspondence and reprint requests to Juliana C.N. Chan, MD, Department of Medicine & Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. E-mail: jchan{at}cuhk.edu.hk
Abstract
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 μmol/l, or doubling of plasma creatinine of baseline value ≥150 μmol/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.
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted September 18, 2004.
- Received November 20, 2003.
- DIABETES CARE
