Association of Genetic Polymorphism in Apolipoprotein A5 and Lipoprotein Lipase Genes with Type Ii Diabetes Mellitus Patients in Rural South Western Maharashtra

Abstract

The most commonly found type of diabetes in India is type II diabetes mellitus (T2DM), which is characterized by decrease in insulin secretion and decrease in insulin sensitivity. Several environmental factors, genetic factors, socio-economic factors, life style, dietary habits have contributed to the surge of T2DM cases in India. Numerous genes involved in lipid metabolism are likely to be candidates as the markers for obesity and T2DM. In the present study, single nucleotide polymorphism (SNP) of two genes namely Apolipoprotein A5 (APOA5) and Lipoprotein lipase (LPL) involved in triglyceride metabolism were investigated using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). The control group comprised of non-obese, non-diabetic subjects (n=120) and T2DM cases were divided into obese (n=120), and non-obese (n=120) groups based on their body mass index (BMI). The demographic features between the control and cases were compared using Chi-square distribution. The genotype frequencies of control and cases were compared using analysis of variance (ANOVA) and binary logistic regression analysis (Odds’ ratio (OR) and adjusted Odds’ ratio). It was observed that APOA5 rs3135506 (OR = 0.46 (0.27-0.79); p = 0.007) was negatively associated, while APOA5 rs662799 (OR = 2.22 (1.28-3.84); p = 0.006) was significantly associated in non-obese diabetic patients. APOA5 rs3135506 (OR = 0.03 (0.01-0.06); p < 0.001) was negatively associated and rs662799 (OR = 4.68 (1.47-14.93); p = 0.01) was significantly associated in obese diabetic patients. Both LPL SNPs (rs285 and rs320) were found not to be associated with T2DM. The association of Apo A5 variants with T2DM may be because of post transcriptional inhibition leading to reduced Apo A5 expression or these alleles may be in linkage disequilibrium with alleles which directly affect the functioning of APOA5. The observations indicated that T2DM is a multi-factorial disease with a large number of gene-gene and gene-environment interactions.