FSHR and LHCGR gene-gene interactions are associated with the risk of anovulation in women of the Rostov region (Russia)

Background. Anovulation is a common cause of female infertility. Signal transduction by follicle-stimulating and luteinizing hormones receptors is substantial for the successful reproduction.

Aim: to study the contribution of intergenic interactions of FSHR rs6166 and LHCGR rs2293275 candidate gene variants to the development of anovulation.

Methods. The present study included 208 women from infertile couples who underwent assisted reproductive technologies, including women with anovulation and normally ovulating women with tubal and/or male factor. Women with reduced FSH and/or AMH serum levels were excluded from the study.

Results. The genotypes frequency distribution for FSHR rs6166 and LHCGR rs2293275 gene variants was AA (40%), AG (43%), GG (17%), and AA (9%), AG (52%), GG (39%), respectively. The present study revealed the two-locus FSHR rs6166 AG / LHCGR rs2293275 GG combination associated with the increased risk of anovulation (OR (95% CI) = 2.43 (1.48-4.01), p<0.001) In addition, among women carried genotype LHCGR rs2293275 AA, none experienced anovulation. The present study also revealed differences among women carrying the risk genotype. Anovulatory women with rs6166 AG / rs2293275 GG combined genotype had an increased AMH level, AFC and LH/FSH ratio and a decreased FSH level, compared to normally ovulating women with the same genotype of risk.

Conclusion. Present study proposes that FSHR rs6166 and LHCGR rs2293275 variants are good candidate markers for association studies, and together may provide an effective model for predicting the risk of anovulation.

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