• PMID: 22791757
• Gene Name: FSHB
• Condition: Infertility
• Association: The study shows that 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
• Mutation: FSHB promoter polymorphism(211G3T, rs10835638)
• Population size: 1213
• Population details: 1213 patients
• Sex: Male
• Infertility type: Male infertility
• Associated genes: FSHR

Combined effects of the variants FSHB -211G>T and FSHR 2039A>G on male reproductive parameters

Tüttelmann F, Laan M, Grigorova M, Punab M, Sõber S, Gromoll J.

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. FAU - Tüttelmann, Frank AU - Tüttelmann F AD - Institute of Human Genetics, Centre of Reproductive Medicine and Andrology, University of Münster, Vesaliusweg 12-14, 48149 Münster, Germany. frank.tuettelmann@ukmuenster.de FAU - Laan, Maris AU - Laan M FAU - Grigorova, Marina AU - Grigorova M FAU - Punab, Margus AU - Punab M FAU - Sõber, Siim AU - Sõber S