• PMID: 24718625
• Gene Name: FSHR
• Condition: Oligozoospermia, Azoospermia
• Association: In contrast to the young male cohort, neither FSHR -29G/A nor FSHR haplotypes appeared to systematically modulate the reproductive physiology of oligozoospermic idiopathic infertile patients (n = 641, Estonians; aged 31.5 � 6.0 years). In summary, this is
• Mutation: FSHB -211G/T; FSHR -29G/A, c.2039 A/G (Asn680Ser, exon 10),
• Population size: 1623
• Population details: 1623 (982; Estonians, Latvians, Lithuanians; aged 20.2 � 2.0 years, 641, Estonians; aged 31.5 � 6.0 years)
• Age: 20.2 � 2.0 years
• Sex: Male
• Infertility type: Male infertility
• Associated genes: FSHB, FSHR
• Other associated phenotypes: Oligozoospermia, Azoospermia

Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants: FSHR -29G/A and c.2039 A/G, FSHB -211G/T

Grigorova M, Punab M, Punab AM, Poolamets O, Vihljajev V, Zilaitien? B, Erenpreiss J, Matulevi?ius V, Laan M.

Follicle-Stimulating Hormone Receptor (FSHR) -29G/A polymorphism (rs1394205) was reported to modulate gene expression and reproductive parameters in women, but data in men is limited. We aimed to bring evidence to the effect of FSHR -29G/A variants in men. In Baltic young male cohort (n = 982; Estonians, Latvians, Lithuanians; aged 20.2 ± 2.0 years), the FSHR -29 A-allele was significantly associated with higher serum FSH (linear regression: effect 0.27 IU/L; P = 0.0019, resistant to Bonferroni correction for multiple testing) and showed a non-significant trend for association with higher LH (0.19 IU/L) and total testosterone (0.93 nmol/L), but reduced Inhibin B (-7.84 pg/mL) and total testes volume (effect -1.00 mL). Next, we extended the study and tested the effect of FSHR gene haplotypes determined by the allelic combination of FSHR -29G/A and a well-studied variant c.2039 A/G (Asn680Ser, exon 10). Among the FSHR -29A/2039G haplotype carriers (A-Ser; haplotype-based linear regression), this genetic effect was enhanced for FSH (effect 0.40 IU/L), Inhibin B (-16.57 pg/mL) and total testes volume (-2.34 mL). Finally, we estimated the total contribution of three known FSH-action modulating SNPs (FSHB -211G/T; FSHR -29G/A, c.2039 A/G) to phenotypic variance in reproductive parameters among young men. The major FSH-action modulating SNPs explained together 2.3%, 1.4%, 1.0 and 1.1% of the measured variance in serum FSH, Inhibin B, testosterone and total testes volume, respectively. In contrast to the young male cohort, neither FSHR -29G/A nor FSHR haplotypes appeared to systematically modulate the reproductive physiology of oligozoospermic idiopathic infertile patients (n = 641, Estonians; aged 31.5 ± 6.0 years). In summary, this is the first study showing the significant effect of FSHR -29G/A on male serum FSH level. To account for the genetic effect of known common polymorphisms modulating FSH-action, we suggest haplotype-based analysis of FSHR SNPs (FSHR -29G/A, c.2039 A/G) in combination with FSHB -211G/T testing. FAU - Grigorova, Marina AU - Grigorova M AD - Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. FAU - Punab, Margus AU - Punab M AD - Andrology Unit, Tartu University Hospital, Tartu, Estonia. FAU - Punab, Anna Maria AU - Punab AM AD - Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. FAU - Poolamets, Olev AU - Poolamets O AD - Andrology Unit, Tartu University Hospital, Tartu, Estonia. FAU - Vihljajev, Vladimir AU - Vihljajev V AD - Andrology Unit, Tartu University Hospital, Tartu, Estonia. FAU - Zilaitienė, Birutė AU - Zilaitienė B AD - Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Erenpreiss, Juris AU - Erenpreiss J AD - Andrology Laboratory, Riga Stradins University, Riga, Latvia. FAU - Matulevičius, Valentinas AU - Matulevičius V AD - Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.