Exploring genotype-phenotype correlation of FSHR polymorphisms in polycystic ovary syndrome.

Purpose: Single nucleotide polymorphisms (SNPs) in FSHR were reported to increase PCOS susceptibility. The present study was conducted to analyse the association of FSHR polymorphisms (rs1394205, rs11692782, and rs2349415) with PCOS in Punjab, India.

Methods: A case-control study comprised of 823 women (443 PCOS cases and 380 healthy controls). Along with anthropometric measurements, lipid and hormonal profiles (LH, FSH, and testosterone levels) were also recorded. The genotyping of FSHR polymorphisms was performed with PCR-RFLP method. Continuous variables were compared using the student's t-test while the genetic association analysis was performed utilizing chi-square, binary logistic regression, and odds ratio with a 95% confidence interval. All the statistical analyses were performed on SPSS v.21 and GraphPad 9.

Results: A significant association of rs2349415 polymorphism was observed with PCOS. The recessive model conferred higher PCOS risk (Adjusted OR-1.64, p = 0.012). The genetic association of rs1394205 and rs11692782 remained non-significant (p > 0.05). rs2349415 and rs1394205 were significantly related to dyslipidemia, while rs11692782 had shown a role in the modulation of gonadotropic hormones. Haploview analysis showed a modest linkage disequilibrium in the block of 133 kb, and no association of FSHR haplotypes was identified with PCOS.

Conclusion: The present findings concluded that a polymorphism, rs2349415, has a significant role in PCOS in the Punjabi population. Also, variations in the FSHR significantly modulate lipid metabolism and hormonal levels.