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Abstract: Introduction: Hypertension and dyslipidemia have been associated with cardiovascular disease (CVD). We investigated the association of candidate gene polymorphisms in angiotensin-converting enzyme (ACE) and cholesterol ester transfer protein (CETP) genes in a cohort of Asian Indian patients with and those without type 2 diabetes. Methods: PCR-based genotyping of insertion/deletion (I/D) polymorphism of ACE (rs4646994) and –629C>A of CETP (rs1800775) was carried out in 520 individuals, of whom 160 had CVD+type 2 diabetes mellitus (T2DM), 90 were CVD patients without T2DM, 150 had T2DM with no cardiovascular complications, and 120 were age- and sex-matched healthy controls. Results: With respect to the ACE gene I/D polymorphism, there was a higher percentage of D/D genotype in CVD+T2DM patients, but it was not statistically significant, while the CETP –629A allele was significantly associated with CVD+T2DM patients (P=.000007; odds ratio=0.46; 95% confidence interval=0.32–0.65) as compared with the normal controls and not with CVD alone. Additive interactions between the AA+I/I genotypes, AC+I/D genotypes, and AC+D/D were identified between the patients and the controls with P values of .0052, .0009, and .0078, respectively. Conclusions: Our study suggests that candidate gene polymorphism –629C>A of CETP may serve as a susceptibility biomarker for CVD in T2DM patients. Analyzing the combined effect of both ACE and CETP genotypes would enhance the sensitivity and specificity of CVD risk estimation in the T2DM patients in our population. [Copyright &y& Elsevier]