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

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, chi(2)-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.