Association of pre-and postnatal mercury exposure with cardiometabolic risk factors in children: the role of the telomere length and telomerase reverse transcriptase polymorphisms

Abstract

Mercury (Hg), particularly methylmercury (MeHg), is a widespread environmental toxicant linked to early-life cardiometabolic risk. This study examined associations between pre-and postnatal total blood mercury (THg) exposure and cardiometabolic outcomes in children, exploring telomere length (TL) as a potential mediator and polymorphisms in the TERT and CLPTM1L genes as effect modifiers. The analysis included 1,301 mother-child pairs from six European cohorts in the HELIX project. THg was measured in maternal and child blood to assess prenatal and postnatal exposure. Cardiometabolic outcomes, including BMI, waist circumference, blood pressure, lipid profile, insulin, and a metabolic syndrome (MetS) risk score, were evaluated in children aged 6-12. TL was measured by quantitative PCR, and polymorphisms in TERT and CLPTM1L were assessed by genome-wide genotyping. Models adjusted for sociodemographic and lifestyle variables, with sensitivity analyses including other environmental contaminants (PCBs, DDE, As, Cd, Pb, Se). Prenatal THg exposure was positively associated with insulin levels, waist circumference, systolic blood pressure, and MetS risk score. Postnatal THg exposure was negatively associated with waist circumference, diastolic blood pressure and hypertension prevalence. TL was inversely associated with adiposity and blood pressure but showed minimal mediation, with only a marginal effect on BMI. TERT polymorphisms, particularly rs33954691 and rs2853669, significantly modified the association between THg and cardiometabolic outcomes. These results identify the prenatal period as a particularly vulnerable window for MeHg toxicity on cardiometabolic risk factors. These associations were largely independent of TL, though genetic variants in TERT altered susceptibility. Future research should explore additional biological pathways beyond telomere dynamics.