Document Detail

Periconceptional multivitamin intake during early pregnancy, genetic variation of acetyl-N-transferase 1 (NAT1), and risk for orofacial clefts.
MedLine Citation:
PMID:  15523664     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Periconceptional supplementation of multivitamins that include folic acid have been shown to prevent several birth defects, including neural tube defects and orofacial clefts. We investigated whether polymorphic variants of fetal acetyl-N-transferase 1 (NAT1), an enzyme involved in the catabolism of folates, differentially interacted with maternal multivitamin use during early pregnancy to alter the risk of delivering an infant with an orofacial cleft malformation. METHODS: Using a large population-based case-control study, we genotyped 421 California infants born with an isolated cleft and 299 controls for two NAT1 polymorphisms. RESULTS: Compared to the homozygous wild-type genotypes, odds ratios for isolated cleft lip with/without cleft palate were slightly increased among infants who were homozygous for the variant alleles of NAT1 1088 and 1095. For isolated cleft palate, no similar associations with these two NAT1 variants were observed. For NAT1 1088 genotypes, we did not observe any differential risks for clefts related to maternal multivitamin intake. For NAT1 1095 genotypes, however, we found a two-fold higher risk for isolated cleft lip with/without cleft palate among infants who were homozygous for the variant allele and whose mothers did not take multivitamins during early pregnancy. CONCLUSIONS: We found evidence suggestive of an interaction between the NAT1 1095 polymorphism and lack of maternal multivitamin use that increased risks of isolated cleft lip with/without cleft palate.
Edward J Lammer; Gary M Shaw; David M Iovannisci; Richard H Finnell
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  70     ISSN:  1542-0752     ISO Abbreviation:  Birth Defects Res. Part A Clin. Mol. Teratol.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-16     Completed Date:  2005-04-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  846-52     Citation Subset:  IM    
Children's Hospital Research Institute, Oakland, California 94609, USA.
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MeSH Terms
Arylamine N-Acetyltransferase / genetics*
Case-Control Studies
Cleft Lip / enzymology,  genetics*
Cleft Palate / enzymology,  genetics*
Cohort Studies
Dietary Supplements
Folic Acid / administration & dosage*
Genetic Variation*
Infant, Newborn
Polymorphism, Genetic / genetics
Preconception Care*
Risk Factors
Grant Support
Reg. No./Substance:
0/Isoenzymes; 59-30-3/Folic Acid; EC N-Acetyltransferase; EC 1

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

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