Effects of a Polymorphism in the Promoter Region of the Follicle-Stimulating Hormone Subunit Beta (FSHB) Gene on Female Reproductive Outcomes

Genet Test Mol Biomarkers. 2019 Jan;23(1):39-44. doi: 10.1089/gtmb.2018.0182. Epub 2018 Dec 26.

Abstract

Background: Follicle-stimulating hormone (FSH) is essential to the hypothalamic-pituitary-gonadal axis, playing a key role in human reproduction. It is a heterodimer comprised of a hormone-specific β-chain (FSH-β) that is associated with an α-chain. It exerts its biological activities by binding to the FSH receptor (FSHR). The β-subunit, which is encoded by the FSHB gene, is responsible for ensuring binding specificity to the FSHR. There is a promoter polymorphism in this gene, c.-211G>T (rs10835638), upstream of the transcription start site; and in vitro studies have reported that the T allele decreases FSHB transcription in gonadotrophic cells.

Aims: Investigate the possible effects of the FSHB c.-211G/T polymorphism on hormonal profile and in in vitro fertilization (IVF)/intracytoplasmic sperm injection outcomes in normoovulatory Brazilian women.

Methods: A cross-sectional study of 140 women (median age = 33 years [CI: 32-34]) with infertility mainly caused by male (n = 85) or tuboperitoneal (n = 55) factors. In this study we evaluated FSH, estradiol, luteinizing hormone (LH), progesterone, prolactin and anti-Mullerian hormone levels, and antral follicle counting (AFC). Genotyping was performed using the TaqMan real-time polymerase chain reaction methodology.

Results: The wild-type allele G was found in 86.4% and the polymorphic allele T in 13.6% of the women respectively. The TT genotype was not found in any women. Women carrying the GT genotype had a poorer response more frequently to controlled ovarian hyperstimulation when compared to individuals with the GG genotype (47.4% vs. 26.5%, p = 0.010), higher LH levels (3.1 IU/mL vs. 2.4 IU/mL, p = <0.001), lower AFC (8.0 vs. 10.0, p = 0.03), oocytes retrieved (3.0 vs. 5.0, p = 0.03), MII (3.0 vs. 4.0, p = 0.02), and embryos (2.0 vs. 3.0, p = 0.02). Despite these findings, no difference was observed in pregnancy rate.

Conclusion: Our findings suggest that the FSHB c.-211G/T polymorphism may modestly alter some aspects of the female reproductive system, but they are not associated with significantly different IVF outcomes.

Keywords: fertilization; FSHB; infertility; polymorphism.

MeSH terms

  • Adult
  • Alleles
  • Anti-Mullerian Hormone / genetics
  • Brazil
  • Carrier Proteins / genetics*
  • Cross-Sectional Studies
  • Female
  • Fertilization in Vitro
  • Follicle Stimulating Hormone / genetics
  • Follicle Stimulating Hormone / metabolism
  • Follicle Stimulating Hormone, beta Subunit / genetics
  • Gene Frequency / genetics
  • Genotype
  • Glycopeptides / genetics*
  • Humans
  • Luteinizing Hormone / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Pregnancy Rate
  • Promoter Regions, Genetic / genetics
  • Receptors, FSH
  • Reproductive Health

Substances

  • Carrier Proteins
  • FSH-BI protein, human
  • Follicle Stimulating Hormone, beta Subunit
  • Glycopeptides
  • Receptors, FSH
  • Anti-Mullerian Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone