Journal article
Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study
Genetic epidemiology, Vol.33(3), pp.247-255
04/2009
DOI: 10.1002/gepi.20376
PMCID: PMC2677659
PMID: 19048631
Abstract
An increased risk of facial clefts has been observed among mothers with lower intake of folic acid or vitamin A around conception. We hypothesized that the risk of clefts may be further moderated by genes involved in metabolizing folate or vitamin A. We included 425 case-parent triads in which the child had either cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO), and no other major defects. We analyzed 108 SNPs and one insertion in 29 genes involved in folate/one-carbon metabolism and 68 SNPs from 16 genes involved in vitamin A metabolism. Using the Triad Multi Marker (TRIMM) approach we performed SNP, gene, chromosomal region, and pathway-wide association tests of child or maternal genetic effects for both CL/P and CPO. We stratified these analyses on maternal intake of folic acid or vitamin A during the periconceptional period.
As expected with this high number of statistical tests, there were many associations with p-values < 0.05; although there were fewer than predicted by chance alone. The strongest association in our data (between fetal
FOLH1
and CPO, p=0.0008) is not in agreement with epidemiologic evidence that folic acid reduces the risk of CL/P in these data, not CPO. Despite strong evidence for genetic causes of oral facial clefts and the protective effects of maternal vitamins, we found no convincing indication that polymorphisms in these vitamin metabolism genes play an etiologic role.
Details
- Title: Subtitle
- Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study
- Creators
- Abee L Boyles - Epidemiology Branch, NIEHS/NIH, Durham, NCAllen J Wilcox - Epidemiology Branch, NIEHS/NIH, Durham, NCJack A Taylor - Epidemiology Branch, NIEHS/NIH, Durham, NCMin Shi - Biostatistics Branch, NIEHS/NIH, Durham, NCClarice R Weinberg - Biostatistics Branch, NIEHS/NIH, Durham, NCKlaus Meyer - Department of Pharmacology, University of Bergen, Bergen, NorwayÅse Fredriksen - Department of Pharmacology, University of Bergen, Bergen, NorwayPer Magne Ueland - Department of Pharmacology, University of Bergen, Bergen, NorwayAnne Marte W Johansen - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, NorwayChristian A Drevon - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, NorwayAstanand Jugessur - Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, AustraliaTruc Trung Nguyen - Department of Public Health and Primary Health Care, University of Bergen, NorwayHåkon K Gjessing - Department of Public Health and Primary Health Care, University of Bergen, NorwayStein Emil Vollset - Department of Public Health and Primary Health Care, University of Bergen, NorwayJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IAKaare Christensen - Center for Prevention of Congenital Malformation, Epidemiology Unit, University of Southern Denmark, Odense, DenmarkRolv T Lie - Department of Public Health and Primary Health Care, University of Bergen, Norway
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.33(3), pp.247-255
- DOI
- 10.1002/gepi.20376
- PMID
- 19048631
- PMCID
- PMC2677659
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Language
- English
- Date published
- 04/2009
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025370302771
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