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

PLoS One. 2014 Apr 9;9(4):e94244. doi: 10.1371/journal.pone.0094244. eCollection 2014.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Alleles
  • Baltic States
  • Follicle Stimulating Hormone, Human / blood*
  • Follicle Stimulating Hormone, beta Subunit / genetics
  • Follicle Stimulating Hormone, beta Subunit / physiology*
  • Genetic Variation
  • Haplotypes
  • Humans
  • Inhibins / blood*
  • Male
  • Oligospermia / blood
  • Oligospermia / ethnology
  • Oligospermia / genetics*
  • Organ Size
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptors, FSH / genetics
  • Receptors, FSH / physiology*
  • Testis / pathology*
  • Testosterone / blood*
  • Young Adult

Substances

  • 5' Untranslated Regions
  • Follicle Stimulating Hormone, Human
  • Follicle Stimulating Hormone, beta Subunit
  • Receptors, FSH
  • inhibin B
  • Testosterone
  • Inhibins