Genetic polymorphisms in the aryl hydrocarbon receptor signaling pathway as potential risk factors of menopausal hot flashes.

Abstract

We sought to determine if genetic polymorphisms in the aryl hydrocarbon receptor signaling pathway are associated with menopausal hot flashes via hormone levels. Women (n = 639) aged 45-54 years completed a study survey and provided blood for genetic and hormone analyses. The associations were analyzed using multivariable logistic regression and generalized linear models. Women carrying CYP1B1 (rs1800440) GG genotype had 3-fold greater odds of experiencing hot flashes for ≥1 year compared to the AA genotype (adjusted odds ratio [OR], 3.05; 95% confidence interval [CI], 1.12-8.25). Adding serum estradiol concentrations to the confounder-adjusted model resulted in a nonsignificant association (adjusted OR, 2.59; 95% CI, 0.91-7.18). Carriers of both CYP1B1 (rs1800440) G and CYP1B1 (rs1058636) G alleles had higher odds of experiencing hot flashes for ≥1 year compared to women homozygous for the major alleles (adjusted OR, 1.77; 95% CI, 1.06-2.96), even after adjustment for serum estradiol. CYP1B1 is associated with menopausal hot flashes via pathways that may involve changes in serum estradiol concentration.