Hwang S J, Beaty T H, Panny S R, Street N A, Joseph J M, Gordon S, McIntosh I, Francomano C A
Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205.
Am J Epidemiol. 1995 Apr 1;141(7):629-36. doi: 10.1093/oxfordjournals.aje.a117478.
In this study of infants with isolated birth defects, 69 cleft palate only cases, 114 cleft lip with or without cleft palate cases, and 284 controls with noncleft birth defects (all born in Maryland between 1984 and 1992) were examined to test for associations among maternal exposures, genetic markers, and oral clefts. A significantly higher frequency of positive family history of birth defects among both groups of oral cleft cases compared with controls was seen in these data. While there was a modest increase in the less common C2 allele at the TaqI site in the transforming growth factor alpha (TGF alpha) locus among cleft palate only infants compared with the birth defect controls, the association appeared to reflect an underlying interaction between maternal smoking and infant genotype. This apparent gene-environment interaction was also found among those reporting no family history of any birth defect. Infants carrying the rarer C2 allele who were exposed to maternal smoking of 10 or fewer cigarettes per day showed a 6.16-fold increase in risk for cleft palate only (95% confidence interval 1.09-34.7), while similar infants whose mothers smoked more than 10 cigarettes per day showed an 8.69-fold higher risk (95% confidence interval 1.57-47.8). However, the dose-response relation was not significant.
在这项针对患有孤立性出生缺陷婴儿的研究中，对69例单纯腭裂病例、114例唇裂伴或不伴腭裂病例以及284例患有非腭裂出生缺陷的对照婴儿（均于1984年至1992年在马里兰州出生）进行了检查，以测试母亲暴露因素、基因标记与口腔裂隙之间的关联。在这些数据中，与对照组相比，两组口腔裂隙病例中出生缺陷家族史呈阳性的频率显著更高。虽然与出生缺陷对照组相比，单纯腭裂婴儿中转化生长因子α（TGFα）基因座TaqI位点较不常见的C2等位基因频率有适度增加，但这种关联似乎反映了母亲吸烟与婴儿基因型之间的潜在相互作用。在那些报告无任何出生缺陷家族史的婴儿中也发现了这种明显的基因 - 环境相互作用。携带较罕见C2等位基因且母亲每天吸烟10支或更少的婴儿，其单纯腭裂风险增加了6.16倍（95%置信区间1.09 - 34.7），而母亲每天吸烟超过10支的类似婴儿，其风险高出8.69倍（95%置信区间1.57 - 47.8）。然而，剂量反应关系并不显著。
