Associations of Estrogen Receptor 1 and Vitamin D Receptor Gene Polymorphisms with Bone Resorption During Pregnancy and Early Postpartum in a Mexican Cohort

BACKGROUND: Pregnancy induces significant changes in calcium metabolism and bone turnover. Genetic variation in estrogen (ESR1) and vitamin D (VDR) receptors may modulate maternal skeletal adaptation, but evidence in pregnancy and the postpartum period is limited. AIMS: To evaluate the association between single nucleotide polymorphisms (SNPs) in the ESR1 and VDR genes and maternal bone resorption during pregnancy and early postpartum in a Mexican cohort. METHODS: We analyzed data from 575 women participating in the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) cohort. Urinary N-telopeptide of type I collagen (NTx) was measured in each trimester and at one month postpartum to assess bone resorption. Six SNPs were genotyped (ESR1: rs9340799, rs2234693, and rs3798577; VDR: rs731236, rs1544410, and rs7975232) and associations were estimated using random-effects regression and generalized additive models, adjusting for age, primigravidity, hematocrit, calcium and energy intake, breastfeeding status, and pregnancy stage. RESULTS: The rs731236 CC genotype (VDR, TaqI) was associated with a significantly lower NTx level (≈ 24% reduction; p = 0.005), indicating a protective effect. None of the other loci were found to have a significant effect on bone resorption. CONCLUSION: Genetic variation in VDR (rs731236) was associated with lower maternal bone resorption during pregnancy and early postpartum. This finding highlights the potential relevance of specific genetic markers in understanding individual susceptibility to pregnancy-related bone loss.