Abstract
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.
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.
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.
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.