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Hum. Reprod. Advance Access published online on June 21, 2008
Human Reproduction, doi:10.1093/humrep/den216
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men

Marina Grigorova1, Margus Punab2, Kristo Ausmees2 and Maris Laan1,3

1 Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia Street 23, 51010 Tartu, Estonia 2 Andrology Unit, Tartu University Clinics, Tartu, Estonia

3 Correspondence address. Tel: +372-7375008; Fax: +372-7-420286; E-mail: maris{at}ebc.ee

BACKGROUND: No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters.

METHODS: A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 ± 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia. RESULTS: Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 ± 1.79 IU/l, n = 423) compared with heterozygotes (2.84 ± 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 ± 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 ± 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups.

CONCLUSIONS: The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed.

Key words: human FSHB gene promoter/serum FSH level/men/regulatory single nucleotide polymorphism/testicular and hormonal parameters

Submitted on March 24, 2008; resubmitted on May 7, 2008; accepted on May 13, 2008.


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