CONTEXT: 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. DESIGN AND SETTING: A total of 1213 German men attending an infertility clinic were genotyped by TaqMan assay. PATIENTS: Patients included male partners in infertile couples without known causes for male infertility. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN AND SETTING: A total of 1213 German men attending an infertility clinic were genotyped by TaqMan assay. PATIENTS: Patients included male partners in infertile couples without known causes for male infertility. MAIN OUTCOME MEASURES: 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.
Authors: A Barbonetti; A E Calogero; G Balercia; A Garolla; C Krausz; S La Vignera; F Lombardo; E A Jannini; M Maggi; A Lenzi; C Foresta; A Ferlin Journal: J Endocrinol Invest Date: 2018-02-01 Impact factor: 4.256
Authors: L Tamburino; S La Vignera; V Tomaselli; R A Condorelli; L M Mongioì; A E Calogero Journal: J Assist Reprod Genet Date: 2017-03-09 Impact factor: 3.412
Authors: G Collodel; S Cantara; G Di Cairano; E Moretti; S Taglianetti; Furio Pacini Journal: J Assist Reprod Genet Date: 2013-07-25 Impact factor: 3.412