Association ofPON1 andAPOA5 Gene Polymorphisms in a Cohort of Indian Patients Having Coronary Artery Disease With and Without Type 2 Diabetes

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.

Importance of Gene Polymorphisms in Renal Transplant Patients to Prevent Post Transplant Diabetes

“…Subsequent studies confirmed the association of this polymorphism in multi ethnic groups [19][20][21]24,25]. A large meta-analysis from 35 studies concerning the IVS3C>T polymorphism which include 33,135 cases of T2DM and 36,316 controls, showed a notable association of this polymorphism with T2DM with the CT heterozygotes carrying just over a 1.4-fold increased risk of T2DM, and TT homozygous variants a 2.0-fold increase in T2DM risk when compared with CC homozygotes [26].…”

“…TCF7L2 gene is expressed in human pancreas, suggesting direct effects on normal β-cell insulin secretion or, more likely, β-cell growth and differentiation from the precursor cells [21]. A report suggests that this genetic variation increases TCF7L2 expression in the β-cell, reducing insulin secretion and predisposing the subject to diabetes [22].…”

APOA5 -1131T>C and APOC3 -455T>C polymorphisms are associated with an increased risk of coronary heart disease

“…Next, we excluded 14 cohort studies, 22 studies not relevant to APOA5 and APOC3, 12 studies unrelated to CHD, and 5 studies containing insufficient information. Finally, 11 case-control studies (Bassi et al, 2003;Bi et al, 2004;Olivieri et al, 2005;Hsu et al, 2006;Zhu et al, 2007;Yu et al, 2007;Martinelli et al, 2007;Li et al, 2007;Jang et al, 2009;De Caterina et al, 2011;Bhaskar et al, 2011) published between 2003 and 2011 (containing in total 4840 CHD patients in the case group and 4913 healthy controls in the control group) were eventually selected for this meta-analysis. Of these, 7 studies involved Asian populations, with 5 conducted in China, 1 in Korea, and 1 in India.…”

Radioprotectors and Mitigators: Current Status

“…Some of them were also found to be risk factors for hypertriglyceridemia, metabolic syndrome, cardio-and cerebrovascular diseases like ischemic stroke, CAD [57,58,[60][61][62][63][64][65][66][67][68][69][70][71]. In a cohort of Indian patients, rs662799 C allele was shown to associate significantly with CAD-T2DM phenotype compared with CAD without T2DM [72]. On the basis of the results of a study conducted on T2DM patients with cerebral infarction Li et al concluded that rs662799 C allele confers independent genetic risk for T2DM with cerebral infarction [73].…”