Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: Evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts
Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: Evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts
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DOI：
10.1002/(sici)1096-9926(199901)59:1
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Murray, JC
中科院分区：
文献类型：
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作者：
Romitti, PA;Lidral, AC;Murray, JC
以往的研究表明，基因与非综合征性唇腭裂(CLP)或单纯唇裂(CP)之间的关系可能会受到环境的影响。利用基于人群的病例对照研究数据，我们研究了转化生长因子α(TGFA)、转化生长因子β3(TGFB3)和MSH(果蝇)同源盒同源物1(Msx1)三个基因的等位基因变异，以及它们与孕期两次暴露(母亲吸烟和饮酒)之间的相互作用，作为CLP和CP的危险因素。对于每一种裂隙表型，与大多数等位基因变异相关的风险估计往往接近统一。母亲吸烟(大于或等于每天10支烟)的风险估计在CP患者中显著升高，并且在TGFB3或Msx1位点具有等位变异的婴儿中升高最明显。相比之下，母亲饮酒(大于或等于4杯/月)的风险估计在CLP中显著升高，在Msx1位点有等位基因变异的婴儿中升高最多。我们的结果表明，母体暴露可能独立地影响CLP和CP的发展，但更显着的是这些暴露和特定等位基因变异的交互作用。畸形学59。1999年，39胜50负。(C)1999年Wiley-Liss，Inc.
Previous studies suggest that the relationship between genes and nonsyndromic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modified by the environment. Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP. For each cleft phenotype, risk estimates associated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (greater than or equal to 10 cigarettes/day) were significantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for maternal alcohol consumption (greater than or equal to 4 drinks/month) were significantly elevated for CLP and were most elevated among infants with allelic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more significantly by interaction of such exposures and specific allelic variants. Teratology 59. 39-50, 1999. (C) 1999 Wiley-Liss, Inc.