Toward a pharmacogenetic approach to male infertility: polymorphism of follicle-stimulating hormone beta-subunit promoter

Objective: To verify in another population (Italians) whether a single-nucleotide polymorphism in the FSHB gene
promoter previously associated with serum FSH levels in Estonians is indeed associated with sperm count and FSH
plasma levels, and especially to verify whether it could be a pharmacogenetic tool for the treatment of male
infertility with FSH.
Design: Cross-sectional and prospective study.
Setting: Infertility center at a university hospital.
Patient(s): Five hundred fourteen subjects with nonobstructive azoospermia and oligozoospermia and 248 subjects
with normozoospermia.
Intervention(s): None.
Main Outcome Measure(s): Semen parameters, reproductive hormone levels, and FSHB 211 G/T polymorphism
(rs10835638).
Result(s): FSHB 211 TT genotype was associated with significantly lower FSH levels (mean SD: 3.3 2.5
IU/L vs. 9.1 8.9 IU/L in GG homozygotes). TT homozygotes were seen in 25% of subjects with azoooligozoospermia
and low FSH levels (%1.5 IU/L). We did not observe this genotype in men with high FSH
levels (>8 IU/L) or in men with normozoospermia. Treatment with FSH induced a significantly higher
improvement in sperm count and quality in TT homozygotes regarding carriers of the G allele.
Conclusion(s): FSHB 211 TT genotype might represent a novel treatable form of male infertility characterized
by severe spermatogenic impairment and low or inappropriately normal FSH plasma levels. This genetic marker
could represent a valid pharmacogenetic approach for identification of potential responders to FSH treatment.