Single Nucleotide Polymorphism analysis of genes FTO, THADA, VEGFÇYP21, CYP11A1 in Polycystic Ovarian Syndrome in Pakistani Population
Authors: Bashir Kashif , Awan Nayab Rasool , Ahmad Mubshra , Saif Sarah , Aziz Zahra 
Published: August 2023

Objectives: The main objective of the study was to evaluate the association of CYP11A1 gene (rs4077582), VEGF (rs1570360), CYP21 gene (rs13405728), FTO (rs9939609), THADA (rs13429458) in PCOS patients. The reason behind the study of selected SNPs was that previously in Pakistan no work on these SNPs has been published yet.
Methods: Blood samples of 600 persons including 300 PCOS patients and 300 controls were collected from different hospitals of Sargodha. DNA was extracted from whole blood samples. To study polymorphism, specific region of DNA was amplified with the help of polymerase chain reaction (PCR). Polymorphic analysis was performed on genes CYP11A1 (rs4077582), VEGF (rs1570360), CYP21 (rs13405728), FTO(rs9939609), THADA (rs13429458) to determine the possible association of with PCOS.
Results: The genotypic association of SNP rs9939609 of FTO, rs13429458 of THADA, rs1570360 VEGF, rs13405728of CYP21 and rs40077582 of CYP11A1 were given in Table 4.2. The heterozygous TA of FTO SNP (rs9939609) show significant association with decreased risk of polycystic ovarian syndrome (OR=0.50; 95% CI= 0.31-0.80; P=0.0038). The mutant AA of the same SNP (rs9939609) did not show any significant association with PCOS (OR=1.23; 95%CI=0.73-2.08; P =0.4261). Combined dominant genotype model (TA+AA) of rs9939609 again show significant association with decreased risk of PCOS (OR=0.42;95%CI=0.23-0.78;P=0.0060) while combined recessive genotype model (TA+TT) did not show any significant association with PCOS (OR= 0..80;95%CI= 0.48-1.36; P=0.4261). In case of gene THADA polymorphism, heterozygous genotype (AC) of showed a significant association with decreased risk of PCOS (OR =0.43; 95%CI= 0.25-0.75; p=0.0027) while homozygous mutant (CC) of same SNP did not show any-significant association (OR=1.26; 95%Cl=0.78-2.04; p=0.3299). Joint genotype model for dominant and recessive did not show any significant association with PCOS(OR=0.78 (95 % CI 0.48-1.27; p=0.3299; OR=0.65; 95 %CI=0.41-1.04; p=0.0781 respectively). The genotypic frequencies of rs1570360 of VEGF gene heterozygote (GA) showed a significant association with increased risk of PCOS by almost 3-folds (OR =2.89, 95%Ci=1.77-4.72; p=0.0001). Same is the case with mutant (AA) which showed highly significant association but with decreased risk of PCOS (OR=0.476; 95%Cl=0.28-0.80; p=0.0051). When the association of Joint genotype model for dominant showed significant association with increased risk of PCOS (OR=2.09; 95%CI=1.24-3.52; p=0.0051) while Joint genotype model for recessive did not show any significant association with PCOS (OR=1.507; 95%CI=0.93-2.42; p=0.0916). Genotypic frequencies of SNPs rs13405728 of CYP21 (LHCGR) gene, heterozygous (CT) showed significant association increase the risk of PCOS by 4-fold (OR=4.10; 95%CI=2.47-6.80; p=0.0001). Situation is same for mutant (TT) which showed significant association with PCOS but with decreased risk (OR=0.27; 95%CI=0.16-0.45; p=0.0001). Joint genotype model for recessive (CT+TT) of this SNP did not show any significant association with PCOS (OR=1.14; 95% CI=0.68-1.92; p=0.59) while Joint genotype model for dominant showed significant association with increased risk of PCOS by 3-folds (OR=3.59; 95% CI=2.52-5.12; p=0.0001). In case of rs4077582 SNP of CYP11A1gene,heterozygous (CT) shows significant association with PCOS with increased risk of 1 fold. The homozygous mutant (TT) of the same SNP did not show any association with the disease (OR=1.377; 95% CI=0.85-2.2; p=0.1855). The combined genotype model for dominant (CT +CC) of the same SNP did not show any significant association with polycystic ovarian syndrome (OR=0.72; 95% CI=0.51-1.01; p=0.06) while combined genotype model for recessive (CT +TT) showed significant association with increased risk of PCOS by 2-folds (OR=2.19; 95% CI=1.35-3.53; p=0.0014).
Conclusion: On the basis of results it is concluded that the hypothesis is accepted. The polymorphism CYP11A1 gene (rs4077582), VEGF (rs1570360), CYP21 gene (rs13405728), FTO (rs9939609), THADA (rs13429458) is associated with PCOS. Allele and some genotypic frequencies in patients and controls are non-significantly associated with PCOS. Our results of the rs13429458 polymorphism shows increasing association between smoking and PCOS.
To conclude PCOS is a combination of complex heredity disorders and previous studies have investigated have many genes for their role as possible loci. By investigating the useful role of this SNP in Pakistani women and building up more information on the genetic basis for PCOS; the establishment of disease in the individuals at risk can be delayed by changing the lifestyle.