The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis

Abstract

BackgroundMale infertility is a complex disorder caused by genetic, developmental, endocrine, or environmental factors as well as unknown etiology. Polymorphisms in the follicle stimulating hormone beta subunit (FSHB) (rs10835638, c.-211G > T) and follicle stimulating hormone receptor (FSHR) (rs1394205, c.-29G > A; rs6165, c.919A > G; rs6166, c.2039 A > G) genes might disturb normal spermatogenesis and affect male reproductive ability.MethodsTo further ascertain the aforementioned effects, we conducted a case-control study of 255 infertile men and 340 fertile controls from South China using the Mass ARRAY method, which was analyzed by the t-tests and logistic regression analysis using SPSS for Windows 14.0. In addition, a meta-analysis was performed by combining our results with previous reports using STATA 12.0.ResultsIn the FSHB or FSHR gene single nucleotide polymorphism (SNP) evaluation, no statistically-significant difference was found in the frequency of allelic variants or in genotype distribution between cases and controls. However, a significant association for the comparison of GAA (P: 0.022, OR: 0.63, 95%CI: 0.43–0.94) was seen between the oligozoospermia and controls in haplotype analysis of rs1394205/rs6165/rs6166. In the meta-analysis, rs6165G allele and rs6166 GG genotype were associated with increased risk of the male infertility.ConclusionsThis study suggested that FSHR GAA haplotype would exert protective effects against male sterility, which indicated that the combination of three SNP genotypes of FSHR was predicted to have a much stronger impact than either one alone. Then in the meta-analysis, a significant association was seen between FSHR rs6165, rs6166 polymorphisms and male infertility. In terms of male infertility with multifactorial etiology, further studies with larger sample sizes and different ethnic backgrounds or other risk factors are warranted to clarify the potential role of FSHB and FSHR polymorphisms in the pathogenesis of male infertility.

Follicle-Stimulating Hormone (FSH) Action on Spermatogenesis: A Focus on Physiological and Therapeutic Roles

“…Although the frequency of allelic variants was similar between the two groups, a specific haplotype was detected more frequently in fertile men (i.e., −29G > A G allele, c.919A > G A allele, and c.2039A > G A allele) [110]. Moreover, a meta-analysis of twelve studies available in the literature confirmed that the presence of either c.919A > G G (p.T307A A) or c.2039A > G G (p.N680S S) alleles is associated to an increased risk of male infertility [110]. This result suggests that different genetic models should be considered for inferring the combinatorial contribution of FSHR SNPs in male infertility, including dominant, co-dominant, and recessive models.…”

“…Therefore, the combination of SNPs modulating the FSHR and FSHB gene transcription and receptor functioning may be predictive of the gonadal response to the hormone in vivo. A recent case-control study evaluated three FSHR SNPs (c.919A > G, c.2039A > G, and c.−29G > A) in 255 infertile men and 340 healthy controls [110]. Although the frequency of allelic variants was similar between the two groups, a specific haplotype was detected more frequently in fertile men (i.e., −29G > A G allele, c.919A > G A allele, and c.2039A > G A allele) [110].…”

“…A recent case-control study evaluated three FSHR SNPs (c.919A > G, c.2039A > G, and c.−29G > A) in 255 infertile men and 340 healthy controls [110]. Although the frequency of allelic variants was similar between the two groups, a specific haplotype was detected more frequently in fertile men (i.e., −29G > A G allele, c.919A > G A allele, and c.2039A > G A allele) [110]. Moreover, a meta-analysis of twelve studies available in the literature confirmed that the presence of either c.919A > G G (p.T307A A) or c.2039A > G G (p.N680S S) alleles is associated to an increased risk of male infertility [110].…”

“…Previous studies examining potential associations between FSHR and FSHB SNPs and male fertility parameters have produced contradictory results, although they suggest that the FSH action on spermatogenesis is likely regulated by a combined effect of many SNPs [110]. Further evidence could be obtained by new studies in which complex haplotypes calculated using several SNPs falling even within genes not involved in the control of the FSH action.…”

“…Further evidence could be obtained by new studies in which complex haplotypes calculated using several SNPs falling even within genes not involved in the control of the FSH action. Moreover, available studies did not collect all fertility-related clinical parameters [110], limiting our current understanding of the impact of SNP combinations on male reproduction. The association between spermatogenetic phenotypes and genetic background could be necessary for developing patient-targeted therapeutic approaches.…”