Hubungan Antara Polimorfisme Gen Hormon Luteinizing Hormone Beta (LHβ) Rs1056917, Follicle Stimulating Hormone Beta (FSHβ) Rs6169, dan Fat Mass And Obesity Associated (FTO) Rs9939609 dengan Sindroma Ovarium Polikistik (SOPK)

Abstract

Introduction: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder associated with ovarian dysfunction, insulin resistance, and obesity. Genetic factors, particularly the LH-β, FSH-β, and FTO genes, play a key role in hormonal and metabolic regulation. The aim of this study was to evaluate the association between LH-β rs1056917, FSH-β rs6169 and FTO rs9939609 genes polymorphisms with PCOS.

Methods: This was an observational analytical study with a case-control design involving PCOS women and healthy controls recruited by consecutive sampling from the Halim Fertility Center Clinic. Genetic polymorphisms were analyzed using PCR and Sanger Sequencing techniques. Data were analyzed using the Chi-square test and odds ratio. Genotype distribution was tested using Hardy-Weinberg Equilibrium (HWE). Clinical variables such as body mass index (BMI), LH/FSH ratio, and HOMA-IR were also evaluated.

Results: The genotype distribution of LH-β rs1056917 showed a significant difference between the PCOS and control groups (p=0.03), with the CC genotype and the presence of the C allele being more dominant in PCOS. The FSH-β rs6169 gene (C and T alleles) and FTO rs9939609 (T and A alleles) did not show a significant direct association with PCOS incidence. The LH-β rs1056917 polymorphism, particularly the C allele, was associated with increased BMI and obesity prevalence, LH/FSH ratio, and insulin resistance (HOMA-IR), but no association was found with the FSH-β rs6169 polymorphism. However, a subanalysis found that the FSH-β rs6169 polymorphism (CT+TT) was associated with BMI and HOMA-IR status. For the FTO rs9939609 gene, although not statistically significant (p>0.05), the AA genotype tended to have higher BMI and HOMA-IR and a greater proportion of insulin resistance in PCOS patients. These genes studied were polymorphic variations and not gene mutations according to the HWE test (p>0.05).

Conclusion: The LH-β rs1056917 gene polymorphism was significantly associated with the incidence of PCOS. The FSH-β rs6169 and FTO rs9939609 genes were not directly related but influenced the patient's metabolic profile. These results strengthen the hypothesis that genetic variants contribute to the pathophysiology of PCOS and have the potential to serve as biomarkers of risk and response to individualized treatment.

Keywords: polycystic ovary syndrome, genetic polymorphism, LH-β rs1056917, FSH-β rs6169, FTO rs9939609