Apolipoprotein C3 Gene Variants and Risk of Developing Type 2 Diabetes in Saudi Subjects

Background: Apolipoprotein C3 (ApoC3) is a major constituent of VLDL and is a modulator of triglyceride metabolism. Recent genetic studies have implicated several ApoC3 gene polymorphisms in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering the high prevalence of T2DM in Saudi Arabia, we sought to examine the possible association of ApoC3 gene variants with diabetes risk in Saudi population. Methods: The 3238C>G and -482C>T polymorphisms of ApoC3 gene were studied in 268 T2DM patients and 255 healthy controls by TaqMan probe based real time polymerase chain reaction assays. Results: Diabetic patients displayed significantly increased systolic blood pressure, fasting plasma glucose, insulin resistance, and dyslipidemia compared to control. Patients also had markedly elevated plasma VLDL levels. Genotype distribution of 3238C>G polymorphism was significantly different between patients and control. Consistently, this variant was found to be significantly associated with T2DM risk. Contrastingly, no significant relationship was found between -482C>T polymorphism and T2DM risk. Association of disease risk with 3238C>G polymorphism remained significant even after accounting for the established risk factors. Genotype-based stratification revealed a significant correlation of GG genotype of 3238C>G with elevated plasma triglycerides, insulin resistance, and VLDL, whereas the TT genotype of -482C>T correlated with elevated triglyceride and VLDL levels. Conclusions: Thus, 3238C>G polymorphism of ApoC3 gene appears to augment the propensity to develop T2DM, while -482C>T to negatively affect lipid metabolism in Saudi subjects.