Association study of FSHR G-29A, 2039A>G, ESR1 (PvuII) showing incident rates of genotypic combinations and it`s correlations with serum hormone FSH, LH, Estradiol levels in patients with primary amenorrhea

Background: Primary amenorrhea is a condition of abnormal menstrual cycle that results into different reproductive diseases. Several functional polymorphisms have been identified in genes that regulate the hypothalamus-pituitary-gonad axis which controls ovarian function. The objective of present study was to analyze the role of genetic variants of HPG axis genes ( FSHR G-29A, 2039A > G and ESR1 (PvuII)) on the severity of clinical features of amenorrhea and disease susceptibility. Methods: In this study, the allelic, genotype and haplotype frequency distributions of three SNPs in the FSHR and ESR1 gene were analyzed in 101 women with primary amenorrhea, and 122 age- and ethnically-matched control individuals. FSHR and ESR1 genotyping were done by Polymerase chain reaction-Restriction length polymorphism and Amplification-Refractory Mutation System method. Genotype distributions were compared between patients and controls. The distribution of the polymorphisms was confirmed by Hardy-Weinberg equilibrium test. Result: A significant increase in luteinizing hormone level in GG genotype of FSHR 2039G > A was observed. However, allelic, genotype and haplotype frequencies of three polymorphisms considering the primary amenorrhea did not differ statistically. Genetic combination analysis also suggests no association in studied SNPs between patients and controls. Limited linkage disequilibrium was noted among FSHR G-29A and 2039A > G. Conclusion: The FSHR 2039G > A polymorphism modulates LH serum levels in primary amenorrhea patients. These findings highlight the importance to pay attention to the association studies of genetic variations associated with clinical-endocrine parameters. However, these findings need to be confirmed in different types of populations.