Effect of Paraoxonase1 (PON1) gene polymorphisms on PON1 activity, HDL, LDL and MDA levels in women with polycystic ovary syndrome (PCOS): A case-control study

Abstract

Polycystic ovary syndrome (PCOS) is considered as one of the most common endocrine disorders in premenopausal women with varied pathophysiology. In this study we investigated the association between -108C/T and 55L/M polymorphisms of Paraoxonase1 (PON1) gene with PCOS. PON1 gene codes for the antioxidant enzyme PON1 which is an HDL associated enzyme that prevents oxidative modification of low-density lipoprotein. A total of 192 women with PCOS and 212 control women from an ethnic population (Kashmir) were included in the study. The PON1 polymorphism was genotyped using PCR-RFLP technique. Clinical, Biochemical parameters were analyzed, and HOMA-IR was used to estimate insulin resistance. Serum PON1 activity and MDA levels were also measured. The frequencies of variant PON1 -108TT genotype and T allele were significantly higher in women with PCOS than controls (31.25%Vs15.09%) and (56.77%Vs41.27%) respectively. The -108TT genotype remained a significant predictor for PCOS (OR-odds ratio = 3.8051, 95%CI = 2.101–6.8914, χ2-chi square = 20.19, P < .05). Fasting insulin and HOMA-IR were significantly raised in PCOS women than controls (P = .000). Serum PON1 activity and HDL-Cholesterol were significantly decreased whereas MDA and LDL-Cholesterol were significantly raised in PCOS women than controls (P = .000). A significant difference was observed between PON1 -108C/T genotypes and weight, waist, waist/hip, BMI, FG score, glucose 1 h, fasting insulin, HOMA, FGIR, QUICKI, LDL-C, testosterone, PON1 activity and MDA (P < .05). Compared with the -108CC genotype, carriers with -108TT genotype of PON1 had significantly raised cholesterol and MDA, and decreased HDL-C and PON1 activity (P < .05). No significant difference was found in the PON1 55L/M genotype and allele frequencies between PCOS women and healthy controls. In conclusion, -108C/T Polymorphism but not 55L/M Polymorphism is a risk factor for PCOS and deranged biochemical, hormonal and lipid profile in Kashmiri women.