Document Detail


Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City.
MedLine Citation:
PMID:  20504979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J Richard Pilsner; Howard Hu; Robert O Wright; Katarzyna Kordas; Adrienne S Ettinger; Brisa N Sánchez; David Cantonwine; Alicia L Lazarus; Alejandra Cantoral; Lourdes Schnaas; Martha Maria Téllez-Rojo; Mauricio Hernández-Avila
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2010-05-26
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  92     ISSN:  1938-3207     ISO Abbreviation:  Am. J. Clin. Nutr.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-07-07     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  226-34     Citation Subset:  AIM; IM    
Affiliation:
Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA. rpils@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Bone and Bones / metabolism
Child, Preschool
Cognition Disorders / chemically induced*,  genetics*
Developmental Disabilities / epidemiology,  genetics*
Dietary Supplements
Energy Intake
Female
Genetic Linkage
Genotype
Haplotypes
Humans
Lead / metabolism
Lead Poisoning / genetics*
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Mexico
Mothers
Parity
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Postpartum Period
Pregnancy
Regression Analysis
Grant Support
ID/Acronym/Agency:
K01 ES014907/ES/NIEHS NIH HHS; K01 ES014907-05/ES/NIEHS NIH HHS; K23 ES000381/ES/NIEHS NIH HHS; P01 ES012874/ES/NIEHS NIH HHS; P30 ES00002/ES/NIEHS NIH HHS; P42 ES05947/ES/NIEHS NIH HHS; R01 ES007821/ES/NIEHS NIH HHS; R01 ES013744/ES/NIEHS NIH HHS; R01 ES014930/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
7439-92-1/Lead; EC 1.5.1.20/Methylenetetrahydrofolate Reductase (NADPH2)
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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