Journal article
Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants
American journal of human genetics, Vol.80(1), pp.76-90
01/2007
DOI: 10.1086/510518
PMCID: PMC1785306
PMID: 17160896
Abstract
Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal NAT2 and CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set, NAT2 continued to show significant overtransmission of an allele to the fetus, with a final P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a GSTT1-null deletion, seen in both the Danish (P=.03) and Iowan (P=.002) studies, with a Fisher's combined P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.
Details
- Title: Subtitle
- Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants
- Creators
- Min Shi - Department of Biology, University of Iowa, Iowa City, IA, 52242, USAKaare ChristensenClarice R WeinbergPaul RomittiLise BathumAnthony LozadaRichard W MorrisMichael LovettJeffrey C Murray
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.80(1), pp.76-90
- DOI
- 10.1086/510518
- PMID
- 17160896
- PMCID
- PMC1785306
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- United States
- Grant note
- P50 DE016215 / NIDCR NIH HHS Intramural NIH HHS R01 DE008559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS R01 DE11948 / NIDCR NIH HHS U50/CCU 71328 / PHS HHS DE08559 / NIDCR NIH HHS R01 DE011948 / NIDCR NIH HHS
- Language
- English
- Date published
- 01/2007
- Academic Unit
- Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Biostatistics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9983995059502771
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