Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women

Climacteric. 2024 Jun;27(3):314-320. doi: 10.1080/13697137.2024.2306269. Epub 2024 Feb 6.

Abstract

Objective: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERβ genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women.

Methods: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERβ. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables.

Results: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty.

Conclusion: The five SNPs of the ERα and ERβ genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Keywords: Frailty; estrogen receptor estrogen receptor; menopause; single nucleotide polymorphisms.

MeSH terms

  • Aged
  • Alleles
  • Cross-Sectional Studies
  • Estrogen Receptor alpha* / genetics
  • Estrogen Receptor beta* / genetics
  • Female
  • Frailty* / genetics
  • Humans
  • Linear Models
  • Middle Aged
  • Phenotype*
  • Polymorphism, Single Nucleotide*
  • Postmenopause* / genetics

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • ESR1 protein, human