Background: Klinefelter syndrome (KS) is the most frequent genetic cause of male infertility. Individuals share the endocrine hallmark of hypergonadotropic hypogonadism, displaying high gonadotropin levels due to deficient testicular function. A single-nucleotide polymorphism (SNP) located within the FSHB promoter region (−211G>T, rs10835638) was recently shown to be associated with reduced serum FSH levels and other reproductive parameters in men. The objective of this study was to analyse the impact of FSHB −211G>T on endocrine and reproductive parameters in untreated and testosterone-treated KS patients.
Subjects & methods: Patients were retrospectively selected from the clientele attending the Department of Clinical Andrology, Centre of Reproductive Medicine and Andrology, University Clinics Münster, a tertiary-referral centre, for couple infertility and andrology. A total of 316 non-mosaic KS individuals between 18 and 65 years were included while excluding higher-grade aneuploidies or mosaic form. Subjects were genotyped for FSHB −211G>T by TaqMan assay. Associations of the single-nucleotide polymorphism genotypes with endocrine and reproductive parameters were assessed.
Results: The untreated group comprised 253 men, in which the FSHB −211G>T T-allele was significantly associated with reduced serum FSH levels (−4.6 U/l per T-allele, P=7.7×10−3). TT-homozygotes displayed 50% lower mean and median FSH levels compared to GG-homozygotes. A non-significant and less pronounced gradient for reduced LH levels over the three genotypes was also observed. Testosterone treatment (n=154) abolished the observed association on FSH levels. When analysing patients before and under testosterone treatment (n=91) gonadotropin levels were similarly suppressed independently of the FSHB genotype.
Conclusions: A hypergonadotropic setting such as KS does not mask the genotype FSHB −211G>T effects on FSH serum levels. The impact was even more pronounced when compared to normal or infertile men, while gonadotropin suppression under testosterone treatment seems to be independent of the genotype. Thus the FSHB −211G>T genotype is a key determinant in the regulation of gonadotropins. pathopyhsiologies.