Maternal smoking and the risk of orofacial clefts

Susceptibility with NAT1 and NAT2 polymorphisms

Edward J. Lammer, Gary M. Shaw, David M. Iovannisci, Janee Gelineau-van Waes, Richard H. Finnell

Research output: Contribution to journalArticle

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Abstract

Background: Orofacial clefts are etiologically heterogeneous malformations. One probable cause is maternal smoking during pregnancy. The effect of maternal smoking may be modified by genes involved in biotransformation of toxic compounds derived from tobacco. We investigated whether polymorphic variants of fetal acetyl-N-transferases 1 (NAT1) and 2 (NAT2) interact with maternal cigarette smoking during early pregnancy to increase the risk of delivering an infant with an orofacial cleft. Methods: In a California population-based case-control study, we genotyped 421 infants born with an isolated cleft and 299 nonmalformed controls for 2 NAT1 and 3 NAT2 single nucleotide polymorphisms Results: Although smoking was independently associated with increased risks for both isolated cleft lip ± cleft palate and isolated cleft palate, no independent associations were found for NAT1 1088 or 1095 genotypes or for NAT2 acetylator status. However, the infant NAT1 1088 and 1095 polymorphisms were strongly associated with the risk of clefts among smoking mothers; infants with NAT1 1088 genotype AA versus TT (odds ratio [OR] = 3.9; 95% confidence interval = 1.1-17.2) and with NAT1 1095 genotype AA versus CC (OR = 4.2; 1.2-18.0). Infant NAT2 acetylator status did not appreciably affect susceptibility of the fetus to the teratogenic effects of maternal smoking. Conclusions: Our results suggest that maternal smoking during pregnancy may increase risk for orofacial clefts particularly among smokers whose fetuses have polymorphic variants of NAT1, an enzyme involved in phase II detoxification of tobacco smoke constituents.

Original languageEnglish
Pages (from-to)150-156
Number of pages7
JournalEpidemiology
Volume15
Issue number2
DOIs
StatePublished - Mar 2004
Externally publishedYes

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Smoking
Mothers
Genotype
Cleft Palate
Pregnancy
Tobacco
Fetus
Phase II Metabolic Detoxication
Odds Ratio
Poisons
Cleft Lip
Biotransformation
Transferases
Smoke
Single Nucleotide Polymorphism
Case-Control Studies
Confidence Intervals
Enzymes
Population
Genes

All Science Journal Classification (ASJC) codes

  • Epidemiology

Cite this

Maternal smoking and the risk of orofacial clefts : Susceptibility with NAT1 and NAT2 polymorphisms. / Lammer, Edward J.; Shaw, Gary M.; Iovannisci, David M.; Gelineau-van Waes, Janee; Finnell, Richard H.

In: Epidemiology, Vol. 15, No. 2, 03.2004, p. 150-156.

Research output: Contribution to journalArticle

Lammer, Edward J. ; Shaw, Gary M. ; Iovannisci, David M. ; Gelineau-van Waes, Janee ; Finnell, Richard H. / Maternal smoking and the risk of orofacial clefts : Susceptibility with NAT1 and NAT2 polymorphisms. In: Epidemiology. 2004 ; Vol. 15, No. 2. pp. 150-156.
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abstract = "Background: Orofacial clefts are etiologically heterogeneous malformations. One probable cause is maternal smoking during pregnancy. The effect of maternal smoking may be modified by genes involved in biotransformation of toxic compounds derived from tobacco. We investigated whether polymorphic variants of fetal acetyl-N-transferases 1 (NAT1) and 2 (NAT2) interact with maternal cigarette smoking during early pregnancy to increase the risk of delivering an infant with an orofacial cleft. Methods: In a California population-based case-control study, we genotyped 421 infants born with an isolated cleft and 299 nonmalformed controls for 2 NAT1 and 3 NAT2 single nucleotide polymorphisms Results: Although smoking was independently associated with increased risks for both isolated cleft lip ± cleft palate and isolated cleft palate, no independent associations were found for NAT1 1088 or 1095 genotypes or for NAT2 acetylator status. However, the infant NAT1 1088 and 1095 polymorphisms were strongly associated with the risk of clefts among smoking mothers; infants with NAT1 1088 genotype AA versus TT (odds ratio [OR] = 3.9; 95{\%} confidence interval = 1.1-17.2) and with NAT1 1095 genotype AA versus CC (OR = 4.2; 1.2-18.0). Infant NAT2 acetylator status did not appreciably affect susceptibility of the fetus to the teratogenic effects of maternal smoking. Conclusions: Our results suggest that maternal smoking during pregnancy may increase risk for orofacial clefts particularly among smokers whose fetuses have polymorphic variants of NAT1, an enzyme involved in phase II detoxification of tobacco smoke constituents.",
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N2 - Background: Orofacial clefts are etiologically heterogeneous malformations. One probable cause is maternal smoking during pregnancy. The effect of maternal smoking may be modified by genes involved in biotransformation of toxic compounds derived from tobacco. We investigated whether polymorphic variants of fetal acetyl-N-transferases 1 (NAT1) and 2 (NAT2) interact with maternal cigarette smoking during early pregnancy to increase the risk of delivering an infant with an orofacial cleft. Methods: In a California population-based case-control study, we genotyped 421 infants born with an isolated cleft and 299 nonmalformed controls for 2 NAT1 and 3 NAT2 single nucleotide polymorphisms Results: Although smoking was independently associated with increased risks for both isolated cleft lip ± cleft palate and isolated cleft palate, no independent associations were found for NAT1 1088 or 1095 genotypes or for NAT2 acetylator status. However, the infant NAT1 1088 and 1095 polymorphisms were strongly associated with the risk of clefts among smoking mothers; infants with NAT1 1088 genotype AA versus TT (odds ratio [OR] = 3.9; 95% confidence interval = 1.1-17.2) and with NAT1 1095 genotype AA versus CC (OR = 4.2; 1.2-18.0). Infant NAT2 acetylator status did not appreciably affect susceptibility of the fetus to the teratogenic effects of maternal smoking. Conclusions: Our results suggest that maternal smoking during pregnancy may increase risk for orofacial clefts particularly among smokers whose fetuses have polymorphic variants of NAT1, an enzyme involved in phase II detoxification of tobacco smoke constituents.

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