Molecular analysis of FSHR rs6166 polymorphism and oxidative stress parameters in women with polycystic ovary syndrome.

BACKGROUND

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder associated with hormonal dysregulation, oxidative stress, and genetic susceptibility. The follicle-stimulating hormone receptor (FSHR) rs6166 polymorphism has been investigated for its potential association with ovarian function and PCOS. In addition, regarding FSHR rs6166 polymorphism in PCOS, limited data are available from Kurdistan Region-Iraqi women.

PURPOSE: Molecular analysis of FSHR rs6166 polymorphism, oxidative stress markers and hormonal profile in women with PCOS. Gene interaction networks, anthropometric and reproductive characteristics of PCOS were another main aim of current study.

METHODOLOGY: Blood samples from PCOS patients and healthy controls were collected for molecular, hormonal and oxidative stress assessments. FSHR rs6166 polymorphism was analyzed by polymerase chain reaction (PCR) and Sanger sequencing. In silico analyses were performed using Genome Aggregation Database (gnomAD) and GeneMANIA databases.

RESULTS

The rs6166 variant was highly prevalent in both PCOS patients (84.21%) and controls (80.00%), predominantly in heterozygous form. Women with PCOS demonstrated significantly reduced follicle-stimulating hormone (FSH), progesterone (PROG), and superoxide dismutase (SOD) levels, alongside elevated estradiol concentrations (p < 0.05). Variant carriers showed lower antioxidant marker levels, particularly SOD and total antioxidant capacity (T-AOC). In silico analysis identified rs6166 as a missense coding variant within the FSHR gene. GeneMANIA predicted interactions between FSHR and multiple genes associated with reproductive function, providing supportive bioinformatic context for the observed associations.

CONCLUSION

FSHR rs6166 polymorphism may associate with PCOS susceptibility through its interaction with reproductive regulatory pathways and oxidative stress imbalance. Gene interaction analysis further supports the potential biological relevance of FSHR in pathways associated with PCOS.