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

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) ER$\alpha$ and ER$\beta$ 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 ER$\alpha$ gene and two in the ER$\beta$. 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 ER$\alpha$ 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 ER$\alpha$ and ER$\beta$ 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.