Maternal smoking during early pregnancy, GSTP1 and EPHX1 variants, and risk of isolated orofacial clefts.
OBJECTIVE
To examine the interactions between four fetal xenobiotic metabolizing gene polymorphisms, maternal cigarette smoking, and risk for oral cleft defects.


METHODS
California population-based case-control study of 431 infants born with isolated orofacial clefts and 299 nonmalformed controls.


METHODS
Infants were genotyped for functional polymorphisms of the detoxification enzymes microsomal epoxide hydrolase-1 (EPHX1 T-->C [Tyr113His], and A-->G [His139Arg]), and glutathione-S transferase Pi-1 (GSTP1 A-->G [Ile105Val] and C-->T [Ala114Val]), and risks for cleft outcomes were measured for gene only and gene-maternal smoking effects.


RESULTS
Although smoking was associated with an increased risk for isolated cleft lip+/-palate, we found no independent associations of genotypes of EPHX1-codon 113 or GSTP1-codon 105 polymorphisms for either isolated cleft lip+/-palate or isolated cleft palate. The heterozygote genotype for the EPHX1-codon 139 polymorphism was associated with an increased risk of isolated cleft palate (odds ratio=1.6 [95% confidence interval, 1.0 to 2.6]). Infant EPHX1 and GTSP1 polymorphic variants did not appreciably alter the risks for clefts associated with maternal smoking, nor were any EPHX1 combined genotype-specific risks found. Infant genotypes of the GSTP1-codon 105 polymorphism, combined with glutathione-S-transferase-mu-1 null genotypes, did not appreciably alter the risk of orofacial clefts.


CONCLUSIONS
Our results suggest that genetic variation of the detoxification enzymes EPHX1 and GSTP1 did not increase the risks of orofacial clefting, nor do they influence the risks associated with maternal smoking.
Ramirez
Dorian
D
Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, and Children's Hospital and Research Center, Oakland, CA 94609, USA.
Lammer
Edward J
EJ
Iovannisci
David M
DM
Laurent
Cecile
C
Finnell
Richard H
RH
Shaw
Gary M
GM
D000328:Adult; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003062:Codon / Q000032:analysis; D004812:Epidemiologic Methods; D004851:Epoxide Hydrolases / Q000032:analysis / Q000235:genetics*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*
D003062:Codon; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human