Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City.
نویسندگان
چکیده
BACKGROUND Maternal folate nutritional status and prenatal lead exposure can influence fetal development and subsequent health. The methylenetetrahydrofolate reductase (MTHFR) gene is important for folate metabolism, and 2 common polymorphisms, C677T and A1298C, reduce enzymatic activity; C677T is present at high penetrance in Mexican populations. OBJECTIVE The objective of this study was to examine potential links between maternal and child MTHFR polymorphisms and child neurodevelopment in a lead-exposed population. DESIGN Data regarding MTHFR polymorphisms C677T and A1298C, peri- and postnatal lead measures, and Bayley Mental Development Index at 24 mo of age (MDI-24) scores were available for 255 mother-child pairs who participated in the ELEMENT (Early Life Exposures in Mexico to Environmental Toxicants) study during 1994-1995. RESULTS In covariate-adjusted regression models, maternal MTHFR 677 genotype predicted MDI-24 scores, in which each copy of the maternal MTHFR 677T variant allele was associated with lower MDI-24 scores (beta = -3.52; 95% CI: -6.12, -0.93; P = 0.004). Maternal MTHFR haplotype also predicted MDI-24 scores (mean +/- SE: 93.3 +/- 1.2 for 677C-1298A compared with 89.9 +/- 0.8 for 677T-1298A; P < 0.05). MDI-24 scores were not associated with maternal MTHFR 1298 genotype or child MTHFR genotypes. We did not observe significant MTHFR genotype x lead interactions with respect to any of the subject biomarkers of lead exposure. CONCLUSIONS The maternal MTHFR 677T allele is an independent predictor of poorer child neurodevelopment at 24 mo. These results suggest that maternal genetic variations in folate metabolism during pregnancy may program offspring neurodevelopment trajectories. Further research is warranted to determine the generalizability of these results across other populations.
منابع مشابه
HFE Gene Variants Modify the Association between Maternal Lead Burden and Infant Birthweight: A Prospective Birth Cohort Study in Mexico City, Mexico
BACKGROUND Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (HFE) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight. METHODS We investigated the role of HFE C282Y, HFE H63 D, and transferrin (TF) P570 S gene variants in modifying the association of lead and ...
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Small size at birth continues to be a problem worldwide and many factors, including reduced folate intake and Pb exposure, are associated with it. However, single factors rarely explain the variability in birth weight, suggesting a need for more complex explanatory models. We investigated environment-gene interactions to understand whether folate intake and maternal Pb exposure were associated ...
متن کاملMaternal Risk Factors Associated with the Development of Cleft Lip and Cleft Palate in Mexico: A Case-Control Study
Introduction: Cleft lip and palate, the most common developmental deformity, is seen worldwide and the etiology involves a combination of genetic and environmental factors. The purpose of this study was to determine the maternal risk factors associated with the development of cleft lip and cleft palate. Materials and Methods: We conducted a case control study at the Women’s Hospital in Culiacan...
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ورودعنوان ژورنال:
- The American journal of clinical nutrition
دوره 92 1 شماره
صفحات -
تاریخ انتشار 2010