Combined effects of the variants FSHB -211G>T and FSHR 2039A>G on male reproductive parameters.
BACKGROUND
A polymorphism in the FSHB promoter (-211G>T, rs10835638) was shown to influence male serum FSH levels, whereas a polymorphism in the FSH receptor gene (FSHR; 2039A>G, rs6166) was previously shown to be associated with FSH levels in women only.


OBJECTIVE
The objective of the study was to analyze the effects of both FSHB -211G>T and FSHR 2039A>G on male reproductive parameters.


METHODS
A total of 1213 German men attending an infertility clinic were genotyped by TaqMan assay.


METHODS
Patients included male partners in infertile couples without known causes for male infertility.


METHODS
An association analysis of single and combined single-nucleotide polymorphism genotypes with clinical parameters was performed.


RESULTS
The FSHB -211G>T T-allele showed significant dosage effects for FSH (-0.51 U/liter per T-allele), LH (0.28 U/liter), and bitesticular volume (-3.2 ml). Statistical significance was enhanced severalfold after a meta-analysis comprising 3017 men. TT carriers were significantly more prevalent among men with lower sperm counts. The FSHR 2039A>G G-allele exhibited nonsignificant trends for associations with higher FSH and reduced testicular volumes. However, in the combined model, FSHR 2039A>G significantly modulated the more dominant effect of FSHB -211G>T on serum FSH and testicular volume among the T-allele carriers.


CONCLUSIONS
By analyzing both single-nucleotide polymorphisms for the first time, we convincingly show that indeed FSHR 2039A>G has an effect also in males. In the proposed model of the combined effects, FSHB -211G>T acts strongly on male reproductive parameters, whereas the FSHR 2039A>G effects were approximately 2-3 times smaller. Clinically this is of importance because oligozoospermic patients carrying unfavorable variants affecting FSH action may benefit from FSH treatment.
Institute of Human Genetics, Centre of Reproductive Medicine and Andrology, University of Münster, Vesaliusweg 12-14, 48149 Münster, Germany. frank.tuettelmann@ukmuenster.de
Frank
F
Tüttelmann
Maris
M
Laan
Marina
M
Grigorova
Margus
M
Punab
Siim
S
Sõber
Jörg
J
Gromoll
D000328:Adult; D005298:Fertility / Q000235:genetics*; D043373:Follicle Stimulating Hormone, Human / Q000097:blood / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007248:Infertility, Male / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics*; D012042:Registries / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors
D043373:Follicle Stimulating Hormone, Human; D011962:Receptors, FSH