Document Detail

Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.
MedLine Citation:
PMID:  18661527     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folate-related genes associated with clefts have, however, often been inconclusive. This study examined four SNPs related to folate metabolism (MTHFR 677 C-->T, MTHFR 1298 A-->C, MTHFD1 1958 G-->A, and TC II 776 C-->G) in a large Irish population to clarify their relationship with clefts. METHODS: Cases and their parents were recruited from major surgical centers performing cleft repairs in Ireland and a support organization. Data on risk factors, medical history, and DNA were collected. Controls were pregnant women from the greater Dublin area (n = 1,599). RESULTS: CLP cases numbered 536 and CPO cases 426 after exclusions. CPO mothers were significantly more likely than controls to be MTHFR 677 TT, OR 1.50 (95% CI: 1.05-2.16; p = .03). Log-linear analysis showed a borderline association (p = .07). Isolated CPO case mothers were significantly more likely than controls to be homozygous for the MTHFD1 1958 G-->A variant, OR 1.50 (95%CI: 1.08-2.09; p = .02). When multiple cases were added, both CPO cases and case mothers were significantly more likely to be AA (p = .02 and p = .007, respectively). The CLP case-control and mother-control analyses also showed significant effects, ORs 1.38 (95% CI: 1.05-1.82; p = .03) and 1.39 (95% CI: 1.04-1.85; p = .03), respectively. CONCLUSIONS: Associations were found for both CPO and CLP and MTHFD1 1958 G-->A in cases and case mothers. MTHFR 677 C-->T could be a maternal risk factor for clefts but the association was not strong. Because multiple comparisons were made, these findings require additional investigation. Given the known association between MTHFD1 1958 G-->A and NTDs, these findings should be explored in more detail.
James L Mills; Anne M Molloy; Anne Parle-McDermott; James F Troendle; Lawrence C Brody; Mary R Conley; Christopher Cox; Faith Pangilinan; David J A Orr; Michael Earley; Eamon McKiernan; Ena C Lynn; Anne Doyle; John M Scott; Peadar N Kirke
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  82     ISSN:  1542-0760     ISO Abbreviation:  Birth Defects Res. Part A Clin. Mol. Teratol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-29     Completed Date:  2008-11-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  636-43     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Amino Acid Substitution / genetics
Case-Control Studies
Cleft Lip / enzymology,  genetics*,  metabolism
Cleft Palate / enzymology,  genetics*,  metabolism
Folic Acid / genetics,  metabolism*
Genetic Predisposition to Disease*
Methylenetetrahydrofolate Reductase (NADPH2) / genetics
Multicenter Studies as Topic
Polymorphism, Single Nucleotide*
Risk Factors
Grant Support
Z01 HD002502-15/HD/NICHD NIH HHS
Reg. No./Substance:
59-30-3/Folic Acid; EC Reductase (NADPH2)

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