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J Clin Endocrinol Metab. 2010 Jan;95(1):100-8. doi: 10.1210/jc.2009-1010. Epub 2009 Nov 6.

Increased Prevalance of the -211 T allele of follicle stimulating hormone (FSH) beta subunit promoter polymorphism and lower serum FSH in infertile men.

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1
Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.

Abstract

CONTEXT:

The human FSHB promoter polymorphism (rs10835638; -211 G/T) has been associated with serum FSH in a cohort of young Estonian men. The minor allele carriers had reduced serum FSH (15.7% in GT heterozygotes; 40% in TT homozygotes) compared with GG homozygotes.

OBJECTIVE:

Because FSH is essential for normal spermatogenesis and fertility, we speculated that abnormalities in FSH action could contribute to male infertility. We sought to study whether genetically inherited constitutively reduced FSH levels may affect male reproduction and replicate the association between rs10835638 and serum FSH among infertile male patients.

DESIGN:

Genotyping of rs10835638 in a cohort of infertile men (n = 1029; Andrology Center of the Tartu University Clinics, Estonia), including idiopathic infertility cases (IIFC; n = 750).

PATIENTS:

Patients included male partners (sperm concentration <20 x 10(6)/ml) of infertile couples failing to conceive a child for 12 months or longer.

RESULTS:

A significant excess of TT homozygotes (1.1 vs. 2.4%) as well as GT heterozygotes (22.4 vs. 25.1%) was detected among infertile men compared with the young male cohort (chi(2) test, P < 0.05). The T allele of rs10835638 was associated with reduced serum FSH (analysis of covariance; full cohort: P = 1.20 x 10(-6), F = 13.8; IIFC: P = 7.70 x 10(-7), F = 14.3) as well as with low FSH to LH ratio (full cohort: P = 1.52 x 10(-11), F = 25.6; IIFC: P = 3.25 x 10(-9), F = 20.4). The median serum FSH levels differed between the GG and TT carriers by 48.5%. All IIFC with TT genotype exhibited low (<1.8) FSH to LH ratio.

CONCLUSIONS:

In perspective, this genetic marker may have clinical significance in molecular diagnostics of male reproductive success and a potential to identify positive responders to FSH treatment.

PMID:
19897680
PMCID:
PMC2823301
DOI:
10.1210/jc.2009-1010
[Indexed for MEDLINE]
Free PMC Article
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