TGF-alpha genotypes, oral clefts, and environmental risk factors: A population-based California study
- CA Birth Defects Monitoring Program, Emeryville, CA (United States)
- Stanford Univ., Palo Alto, CA (United States); and others
Several studies have shown a relation between genetic variation at the TGF-alpha locus and oral clefts. These studies had limited sample sizes and also lacked data on additional factors potentially related to clefting. We investigated the influence on clefting from risk factors, such as maternal smoking, dependent on TFG-alpha genotype. This was accomplished using a large population-bases case-control study of fetuses and liveborn infants with oral clefts among a 1987-89 cohort of California births (N=548,844). To obtain data on potential risk factors, telephone interviews were conducted with mothers of 731 (84.5% of eligible) cleft cases, and 734 (78.2%) nonmalformed controls. DNA was obtained from newborn screening bloodspots and genotyped by using SSCP designed to detect the Taq1 RFLP. Among mothers who completed an interview, genotyping results were available for 571 (78.1%) cases and 640 (87.2%) controls. Compared to controls, the risk estimate for TGF-alpha polymorphism as measured by the odds ratio was: 0.99 (95% confidence interval 0.64, 1.5) for isolated cleft lip {plus_minus}palate; 0.88 (0.33, 2.2) for nonisolated cleft lip {plus_minus}palate; 1.6 (0.94, 2.8) for isolated cleft palate; 1.9 (0.82, 4.3) for nonisolated cleft palate; and 2.2 (0.99, 5.0) for clefts with known etiology. This dataset also revealed 1.4 to 2-fold increased risks for maternal cigarette smoking > 19 cigs/day in early pregnancy. Among these heavy smokers, risk of clefting was even more increased for infants with the TGF-alpha polymorphism. Our data suggest an association between the TGF-alpha uncommon allele and some phenotypic subgroups as well as provide evidence for a genetic-environment interaction between maternal smoking and the variant in the etiology of clefting. The fraction of cases possibly attributed to this interaction, however, was small.
- OSTI ID:
- 133940
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0674
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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