ASSOCIATIONS BETWEEN FAT MASS AND OBESITY ASSOCIATED (FTO) GENE rs9939609 A/T POLYMORPHISM AND POLYCYSTIC OVARY SYNDROME (PCOS) IN SOUTH INDIAN POPULATION

Abstract

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and metabolic complications such as obesity and insulin resistance. The fat mass and obesity-associated (FTO) gene is recognized as a major obesity susceptibility gene and has been implicated in the pathogenesis of PCOS through its role in energy metabolism and body weight regulation. Objective: This study was undertaken to evaluate the association between polymorphisms in the FTO gene and the risk of PCOS among a population of South Indian women. Methods: A case-control study was conducted involving 160 participants (80 women clinically diagnosed with PCOS and 80 healthy controls). Clinical evaluations included Body Mass Index (BMI), and biochemical assays measured levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), fasting glucose, and cholesterol. Genomic DNA was isolated from blood samples using a split-second isolation protocol. Genotyping of the FTO SNP rs9939609 was performed using Tetra-primer Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS PCR). Statistical significance was determined using student t-tests and chi square analysis. Results: PCOS subjects exhibited significantly higher mean BMI (21.77 ± 2.42 kg/m² for control vs. 25.67 ± 3.41 kg/m² PCOS), fasting glucose (112.28 ± 25.19 for control mg/dL vs. 188.1 ± 71.42 mg/dL for PCOS), cholesterol levels (164.91 ± 39.89 mg/dL for control vs 240.31 ± 42.44)  compared to controls. FSH levels were significantly lower in the PCOS group (6.89 ± 2.44 mIU/ml for control vs 4.01 ± 1.38 mIU/ml for PCOS). For the FTO rs9939609 polymorphism, the frequency of the risk A allele was 76% in PCOS patients and 84% in controls, while the T allele frequency was 65% in PCOS patients and 95% in controls. However, statistical analysis revealed no significant difference in the distribution of FTO genotypes or alleles between the groups (p > 0.05). Conclusion: Although clinical and biochemical markers such as increased BMI, glucose, and cholesterol were significantly associated with the syndrome, the FTO rs9939609 polymorphism did not show a statistically significant association with PCOS risk in the South Indian women studied. These findings suggest that FTO variants may act differently across different ethnicities, and further research with larger cohorts is needed to elucidate the genetic architecture of PCOS.