Endocrine Abstracts

Introduction: FSH is a key player in reproductive functions, the expression of its unique subunit FSHB is regulated by the FSHB promoter. Recently, a single nucleotide polymorphism (SNP) at a highly conserved position in the FSHB promoter (rs10835638; −211G>T) has been found to be associated with decreased serum FSH levels in men and with male infertility. Because to date no information is available on possible endocrine consequences of this SNP in women, we conducted this study to analyze well characterized female individuals.

Patients and methods: Three hundred and sixty five normally cycling women undergoing diagnostics prior to assisted reproductive techniques (ART) were included. Anthropometric and endocrine data were assessed. An independent cohort of 438 fertile females was additionally analyzed. Customized TaqMan technology was used to detect the FSHB SNP in DNA extracted from lymphocytes.

Results: Comparing genotyped patients of our study population with controls, allele and genotype frequencies were not different between groups (T-allele: 14.7 vs 16.6%; TT-homozygotes: 2.4 vs 3.4%). However, we observed strong associations of the T-allele with elevated serum FSH (0.99 U/l per T-allele, P=0.006) and LH (1.30 U/l per T-allele, P<0.001). Additionally, T-allele carrier status was significantly associated with a reduced serum progesterone (−1.96 ng/ml per T-allele, P=0.047) in the studied subjects.

Conclusion: This is the first report on genotype-phenotype correlations of rs10835638 in females. Unexpectedly, the association of this SNP with an elevated FSH in our subjects stands in contrast to previous findings in male. On the other hand, elevated LH-levels in T-allele carriers seem to be present also in males. Together with the observed associations of this SNP with progesterone these novel findings could be indicative of a gender specific regulatory feedback mechanism involving sexual steroids and progesterone responsive elements of the FSHB promoter.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.