Elucidating the Molecular Genetics of Genes CYP19A1, CYP17, and FSHR Variants Association in Polycystic Ovarian Syndrome

Association of genes CYP19A1 (rs2414096), CYP17 (rs743572) and FSHR (rs2268361) variants on the susceptibility of developing PCOS was studied. This disease is most common problem faced by Pakistani females. The incidence of this disease has increased last couple of decades but no work on genes involved in PCOS has been done so far in Pakistan. Blood samples of 300 subjects including 150 PCOS cases and 150 age-matched controls were collected from different hospitals of Pakistan. DNA extraction from whole blood was done followed by DNA amplification. Data was collected on a pre-designed questionnaire for age, BMI, smoking status, and family history. Statistical analysis was done using different statistical tools. Homozygous mutant (GG) of rs2414096 SNP of CYP19A1 gene contributes significantly to the decreased risk of PCOS (OR = 0.24; 95% CI = 0.15–0.40; P = 0.0001), while heterozygous (AG) of the same SNP shows positive association with increased PCOS risk up to 2.62 folds (OR = 2.62; 95% CI = 1.60–4.30; P = 0.0001). Combined genotype model (GG+AG) of this SNP again shows significant association with decreased PCOS risk (OR = 0.44; 95% CI = 0.24–0.81; P = 0.0086). In Case of rs743572 polymorphism of CYP17 gene, homozygous mutant (CC) significantly increased the risk of PCOS by 3.2-fold (OR = 3.22; 95% CI = 1.94–4.34; p = 0.0001) while heterozygous (TC) of the same SNP significantly decreased the risk of PCOS (OR = 0.34; 95% CI = 0.20–0.58; p = 0.0001). In rs2268361 variants of FSHR gene, homozygous mutant (TT) significantly decreases the risk of PCOS and plays a protective role (OR = 0.52; 95% CI = 0.33–0.84; p = 0.0072) while heterozygous (CT) of the same SNP significantly increases the risk of PCOS up to 3 folds (OR = 3.46; 95% CI = 1.97–6.07; p = 0.0001). An increased risk of PCOS is associated with the rs2414096, rs743572 and rs2268361 genotype of genes CYP19A1, CYP17 and FSHR respectively.