Association of SELP Polymorphisms with Soluble P-Selectin Levels and Vascular Risk in Patients with Type 2 Diabetes Mellitus: A Case-Control Study

摘要

P-selectin, an adhesion molecule, is encoded by SELP and known as biomarker of endothelial as well as platelet dysfunction. SELP polymorphisms (rs6136, rs6127, and rs6125) and raised levels of soluble P-selectin (sP-selectin) have been associated with several disease conditions. The present study was aimed to determine the association of SELP variants and sP-selectin levels as well as vascular risk in Type 2 diabetes mellitus (T2DM) patients. The frequency of rs6136, rs6127, and rs6125 was assessed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). sP-selectin levels were measured using commercially available kits. Haplotypes were constructed using PHASE software. The data obtained from the above-said analyses was subjected to suitable statistical analyses. sP-selectin levels (ng/ml) were significantly higher in patients as compared to controls (p0.001). Out of total, 22% of patients were found to have very high vascular risk, 43.2% with high vascular risk, while 34.4% with moderate vascular risk. For both rs6136 and rs6127, frequency of variant allele was found to be significantly higher in patients as compared to controls and accounted for 2.4- and 1.5-fold risk of disease development, respectively. CAG was found to be associated with 4.5-fold risk towards disease development. In contrast, AGG was conferring the protective effect. Significantly high sP-levels were observed in patients with homozygous wild genotype of rs6136, all genotypes of rs6127, and heterozygous genotype of rs6125 as compared to respective controls. Significant difference was observed in P-selectin levels within moderate-risk category for rs6136. When compared between the categories, significant difference was observed for rs6136 and rs6127. Furthermore, patients with haplotypes AAA, AGA, and AGG were found to have significantly high sP-selectin levels as compared to controls. Significant difference in sP-selectin levels was observed within very high-risk as well as high-risk category. When compared between the categories, significant difference was observed for AGA and AGG haplotypes. The studied polymorphisms of SELP have shown significant association with sP-selectin levels as well as vascular risk in T2DM patients.