Insulin gene VNTR class III allele is a risk factor for insulin resistance in Kashmiri women with polycystic ovary syndrome

Abstract

PurposePCOS is a complex heterogeneous multifactorial endocrine disorder characterized by anovulation, hyperandrogenism and polycystic ovaries. PCOS affects 5–10% women of reproductive age is also suggested to increase the risk of insulin resistance, cardiovascular disorders and T2DM. The aim of this study was to assess the possible association of INS VNTR polymorphism with PCOS and their phenotype-genotype interactions in Kashmiri women with PCOS. MethodsA total of 349 subjects including 249 cases and 100 age-matched healthy controls were recruited in the study. DNA was extracted from peripheral venous blood from all subjects and association analysis was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype-phenotype correlation analysis was performed to evaluate the association of INS VNTR polymorphism with phenotypic features. ResultsAllele frequency (OR = 0.86, C.I. 0.48–1.54, P = .61) and genotype distribution (P = .79, χ2 = 0.46) showed no significant association between INS VNTR and PCOS. The dominant (OR = 1.21, χ2 = 0.026, P = .871), recessive (OR = 0.83, χ2 = 0.35, P = .549) and heterozygote vs. homozygote (OR = 1.25, χ2 = 0.45, P = .50) genotype model analysis further supported this finding. Genotype-phenotype correlation analysis showed class III allele carrier (I/III + III/III genotype) was significantly associated with increased weight (P = .044), BMI (P = .021) insulin (F) (P = .049) and HOMA IR (P = .02) in recessive model in PCOS women. ConclusionsINS VNTR polymorphism does not increase the risk of PCOS. However, INS VNTR class III allele is associated with elevated BMI and HOMA IR, suggesting its role in the pathogenesis of insulin resistance and obesity in Kashmiri women with PCOS.