ArticleAmerican journal of human genetics2007
Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants.
Article in American journal of human genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 186 citations in OpenAlex.
- Maternal Cigarette Smoking and Cleft Lip and Palate: A Systematic Review and Meta-Analysis.The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association · 2022Pooled it
- Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls.Human reproduction updatePooled it
- Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.Birth defects research. Part A, Clinical and molecular teratology · 2015Trial
- Craniofacial development: genetics, signaling pathways, teratogenic mechanisms, and clinal significance.Molecular biomedicine · 2026Review
- Genetic and Molecular Basis of Cleft Lip and Palate: A Comprehensive Review.Diagnostics (Basel, Switzerland) · 2026Review
- Gene-by-Environment Interactions Involving Maternal Exposures with Orofacial Cleft Risk in Filipinos.Genes · 2025Article
- Association of maternal prenatal phthalate exposure and genetic polymorphisms of metabolic enzyme genes with spontaneous preterm birth: a nested case-control study in China.BMC pregnancy and childbirth · 2025Article
- Association between serum cotinine concentrations on red blood cell folate concentrations in pregnant women and the mediating role of lymphocytes: an NHANES Study.Archives of public health = Archives belges de sante publique · 2025Article
- Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study.BMC pregnancy and childbirth · 2024Article
- MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate.International journal of molecular sciences · 2023Review
- The effect of maternal smoking and alcohol consumption on lip morphology.Journal of orthodontics · 2022Article
- Recent Advances in Nasoalveolar Molding Therapy Using 3D Technology.Craniomaxillofacial trauma & reconstruction · 2022Review
- Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.Current topics in developmental biology · 2022Article
- Genetic Factors in Nonsyndromic Orofacial Clefts.Global medical genetics · 2020Review
- Environmental mechanisms of orofacial clefts.Birth defects research · 2020Review
- Genetics and signaling mechanisms of orofacial clefts.Birth defects research · 2020Review
- Article
- Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors.Frontiers in cell and developmental biology · 2020Review
- Effect of N-Acetyltransferase 2 Genotype on the Pharmacokinetics of Hydralazine During Pregnancy.Journal of clinical pharmacology · 2019Article
- The effect on congenital heart diseases of maternal EPHX1 polymorphisms modified by polycyclic aromatic hydrocarbons exposure.Medicine · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.