Maternal smoking and oral clefts: the role of detoxification pathway genes.
Maternal smoking and oral clefts: the role of detoxification pathway genes.
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DOI：
10.1097/ede.0b013e3181690731
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Vindenes H
中科院分区：
文献类型：
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作者：
Lie RT;Wilcox AJ;Taylor J;Gjessing HK;Saugstad OD;Aabyholm F;Vindenes H
有证据表明，吸烟对唇裂的风险有影响。还有一些假设的途径涉及香烟烟雾中的有毒化学物质的生物效应。我们对1996年至2001年期间出生于挪威的唇腭裂婴儿进行了一项病例对照和家庭三联研究，病例组（n=573）的参与率为88%，对照组（n=763）的参与率为76%。母亲们在婴儿出生三个月后完成了一份问卷。收集父母和子女的DNA，检测与香烟烟雾化合物解毒相关的基因（NAT 1、NAT 2、CYP 1A 1、GSTP 1、GSTT 1和GSTM 1）。对于孤立性唇裂（有或没有腭裂），在孕早期吸烟存在剂量反应效应。优势比从被动吸烟的1.6（95%CI：1.0 - 2.5）上升到每天吸烟超过10支的母亲的1.9（95%CI：0.9 - 4.0）。几乎没有证据表明与腭裂有关。遗传分析使用病例对照和家庭三联体数据。在病例三联体中，我们发现了NAT 2单倍型与孤立性唇裂之间的关联（单剂量的RR为1.6，双剂量的RR为2.5），但几乎没有证据表明与吸烟相互作用。其他基因没有显示出相关性，先前描述的与吸烟的相互作用也没有得到证实。妊娠早期吸烟与唇裂的风险明显相关。这种效果并没有被与香烟烟雾化合物解毒相关的基因变体所改变。
There is evidence for an effect of cigarette smoking on risk of oral clefts. There are also hypothetical pathways for a biological effect involving toxic chemicals in cigarette smoke. We performed a combined case-control and family-triad study of babies born in Norway with oral clefts in the period 1996 to 2001, with 88% participation among cases (n=573) and 76% participation among controls (n=763). Mothers completed a questionnaire three months after birth of the baby. DNA was collected from parents and children, and assayed for genes related to detoxification of compounds of cigarette smoke (NAT1, NAT2, CYP1A1, GSTP1, GSTT1 and GSTM1). For isolated cleft lip (with or without cleft palate) there was a dose-response effect of smoking in the first trimester. The odds ratio rose from 1.6 (95% CI: 1.0 - 2.5) for passive smoking to 1.9 (95% CI: 0.9 - 4.0) for mothers who smoked more than 10 cigarettes per day. There was little evidence of an association with cleft palate. Genetic analyses used both case-control and family-triad data. In case-triads we found an association between a NAT2 haplotype and isolated cleft lip (RR of 1.6 in single dose and 2.5 in double dose), but with little evidence of interaction with smoking. Other genes did not show associations, and previously described interactions with smoking were not confirmed. First-trimester smoking was clearly associated with risk of cleft lip. This effect was not modified by variants of genes related to detoxification of compounds of cigarette smoke.