Implication of genetic factors contributing to insulin resistance in the pathogenesis of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome PCOS is a significant clinical condition as it is a major affliction of women in the reproductive age globally This is a hospital based observational case control study carried on 169 PCOS and 169 control women in age group 20yrs to 40 yrs Clinical history biochemical and hormonal analysis were carried out and molecular analysis was done using Real time polymerase chain reaction The odds ratio and 95 percent confidence interval were calculated using wild type genotypes or alleles as the reference group A p value 0 point 05 was considered to be statistically significant We observed a significant 2 point 88 fold higher risk of AA genotype in the polymorphism rs1801278 of IRS1 gene compared to the TT genotype in women with PCOS vs the control group odds ratio OR 2 point 88 95 percent CI 1 point 43 to 5 point 80 p 0 point 002 We observed a 20 fold increased risk of A allele in the polymorphism rs 689 of INS gene and a 2 point 14 fold increased risk of A allele in the polymorphism rs1801278 of IRS1 gene in PCOS women with insulin resistance than PCOS women who do not have insulin resistance The single nucleotide polymorphisms majorly influenced insulin resistance in PCOS women with elevated insulin fasting glucose and post prandial glucose levels The genotypes also reflected lower insulin sensitivity in PCOS women Gene gene interaction was observed between PPAR G INSR and IRS1 The SNP rs 1801278 of IRS1 gene may be a strong candidate for insulin resistance in PCOS Further studies are required to decipher the exact molecular mechanisms of the polymorphisms on the risk of PCOS newline