ABSTRACT
Type 2 diabetes mellitus (T2DM) is a major cause of coronary artery disease (CAD) and is responsible for a great deal of morbidity and mortality in Asian Indians. Several gene polymorphisms have been associated with CAD and T2DM in different ethnic groups. This study will give an insight about the association of two selected candidate gene polymorphisms; paraoxonase1 (PON1) Q192R and apolipoprotein A5 (APOA5) -1131T>C were assessed in a cohort of South Indian patients having CAD with and without T2DM. Polymerase chain reaction-based genotyping of PON1 Q192R (rs662) and APOA5-1131T>C (rs662799) polymorphism was carried out in 520 individuals, including 250 CAD patients (160 with T2DM and 90 without T2DM), 150 T2DM patients with no identified CAD, and 120 normal healthy sex- and age-matched individuals as controls. The PON1 192RR genotype and R allele frequency were elevated in both CAD and T2DM patients when compared with controls; however, only CAD patients with T2DM showed a statistical significance (p=0.023; OR=1.49; 95% CI: 1.04-2.12) when compared with controls. The APOA5-1131CC genotype and C allele also showed a significant association between the CAD+T2DM patients when compared with CAD without T2DM and healthy controls (p=0.012; OR=1.71; 95% CI: 1.0-2.67). An additive interaction between the PON1 RR and APOA5 TC genotypes was identified between the T2DM and CAD patients (p=0.028 and 0.0382, respectively). PON1 and APOA5 polymorphisms may serve as biomarkers in the South Indian population to identify T2DM patients who are at risk of developing CAD.
Subject(s)
Apolipoproteins A/genetics , Aryldialkylphosphatase/genetics , Coronary Artery Disease/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Polymorphism, Genetic , White People/genetics , Apolipoprotein A-V , Case-Control Studies , Coronary Artery Disease/epidemiology , Coronary Artery Disease/etiology , Diabetes Mellitus, Type 2/epidemiology , Female , Gene Frequency , Genotype , Humans , India/epidemiology , Male , Polymerase Chain Reaction/methodsABSTRACT
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.
