The FSHB −211G>T variant attenuates serum FSH levels in the supraphysiological gonadotropin setting of Klinefelter syndrome

Abstract Klinefelter syndrome (47, XXY) is the most frequent genetic cause of male infertility and individuals share the endocrine hallmark of hypergonadotropic hypogonadism. Single-nucleotide polymorphisms located within the FSHB/FSHR gene were recently shown to impact serum follicle-stimulating hormone (FSH) levels and other reproductive parameters in men. The objective of this study was to analyse the effect of FSHB-211G>T (c.−280G>T, rs10835638) as well as FSHR c.2039G>A (rs6166) and FSHR c.−29G>A (rs1394205) on endocrine and reproductive parameters in untreated and testosterone-treated Klinefelter patients. Patients were retrospectively selected from the clientele attending a university-based andrology centre. A total of 309 non-mosaic Klinefelter individuals between 18 and 65 years were included and genotyped for the variants by TaqMan assays. The untreated group comprised 248 men, in which the FSHB −211G>T allele was significantly associated with the reduced serum follicle-stimulating hormone levels (−6.5 U/l per T allele, P=1.3 × 10−3). Testosterone treatment (n=150) abolished the observed association. When analyzing patients before and under testosterone treatment (n=89), gonadotropin levels were similarly suppressed independently of the FSHB genotype. The FSHR polymorphisms did not exhibit any significant influence in any group, neither on the endocrine nor reproductive parameters. In conclusion, a hypergonadotropic setting such as Klinefelter syndrome does not mask the FSHB −211G>T genotype effects on the follicle-stimulating hormone serum levels. The impact was indeed more pronounced compared with normal or infertile men, whereas 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 in different reproductive-endocrine pathopyhsiologies.

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Testosterone Alexander S Busch,1,3 Frank Tüttelmann,2,3 Michael Zitzmann,1 Sabine Kliesch,1 and Jörg Gromoll

Author Information

1. Centre of Reproductive Medicine and Andrology, University of Münster, Münster, Germany
2. Institute of Human Genetics, University of Münster, Münster, Germany
3. Centre of Reproductive Medicine and Andrology, University Clinics Muenster, Albert-Schweitzer-Campus 1, Building D11, 48149 Muenster, Germany. Tel: +49 251 8356447; Fax: +49 251 354800; E-mail: [email protected] Eur J Hum Genet. 2015 May; 23(5): 700–703.
Published online 2014 Jul 23 PMCID: PMC4402621
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402621/

by Gary Khodanian | May 23, 2015