Association between plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipids with rs7903146 polymorphisms of the TCF7L2 gene in diabetic patients

The rs7903146 polymorphism of TCF7L2 gene is known as the strongest genetic risk factor for type 2 diabetes mellitus (T2DM). The polymorphism is in association with clinical profile of T2DM patients. PCSK9 is a serine protease that promotes LDLR degradation and regulates circulating levels of lipids. The association of this polymorphism with PCSK9 and metabolic profile of diabetic and healthy subjects was investigated. This cross-sectional study was performed on 132 T2DM patients and the same number of healthy subjects. All the participants were genotyped for the rs7903146 single nucleotide polymorphism by the PCR-RFLP method. Metabolic profile including plasma levels of PCSK9, triglycerides, total cholesterol, non-HDL cholesterol, LDL cholesterol, HDL cholesterol, fasting plasma glucose, and HBA1C was measured. PCSK9, total cholesterol, and LDL-C levels were lower in the diabetic patients as compared to the healthy subjects. There were also direct and significant associations between PCSK9 and TG, TC, LDL-C, and non HDL-C in the subjects. Values of plasma glucose, HbA1c, PCSK9, TC, and LDL-C were higher in patients with TT genotype, but the differences were not statistically significant for all. A positive Spearman correlation was found between PCSK9 levels and the genotypes in all the participants. The results confirm the association of rs7903146 in the TCF7L2 gene with metabolic parameters and PCSK9. The T allele was associated with higher lipid and PCSK9 levels.