Centers for Disease Control and Prevention, Atlanta, Georgia.
Am J Med Genet A. 2014 Jun;164A(6):1454-63. doi: 10.1002/ajmg.a.36478. Epub 2014 Mar 25.
Maternal smoking during pregnancy is one proposed risk factor for gastroschisis, but reported associations have been modest, suggesting that differences in genetic susceptibility might play a role. We included 108 non-Hispanic white and 62 Hispanic families who had infants with gastroschisis, and 1,147 non-Hispanic white and 337 Hispanic families who had liveborn infants with no major structural birth defects (controls) in these analyses. DNA was extracted from buccal cells collected from infants and mothers, and information on periconceptional smoking history was obtained from maternal interviews, as part of the National Birth Defects Prevention Study. We analyzed five polymorphisms in three genes that code for enzymes involved in metabolism of some cigarette smoke constituents (CYP1A1, CYP1A2, and NAT2). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) independently for maternal smoking and maternal and infant gene variants, and to assess joint associations of maternal smoking and maternal or infant gene variants with gastroschisis. In analyses adjusted for maternal age at delivery and stratified by maternal race-ethnicity, we identified three suggestive associations among 30 potential associations with sufficient numbers to calculate ORs: CYP1A12A for non-Hispanic white mothers who smoked periconceptionally (aOR = 0.38, 95% CI 0.15-0.98), and NAT26 for Hispanic non-smoking mothers (aOR = 2.17, 95% CI 1.12-4.19) and their infants (aOR = 2.11, 95% CI 1.00-4.48). This analysis does not support the occurrence of effect modification between periconceptional maternal smoking and most of the xenobiotic metabolizing enzyme gene variants assessed.
孕妇在怀孕期间吸烟是导致腹裂的一个已知危险因素，但已报告的相关性并不显著，这表明遗传易感性的差异可能起作用。在这些分析中，我们纳入了 108 个非西班牙裔白人和 62 个西班牙裔家庭，这些家庭的婴儿患有腹裂，以及 1147 个非西班牙裔白人和 337 个西班牙裔家庭，这些家庭的活产婴儿没有主要的结构性出生缺陷（对照）。作为国家出生缺陷预防研究的一部分，从婴儿和母亲的口腔细胞中提取 DNA，并通过母亲访谈获得围孕期吸烟史的信息。我们分析了三个编码参与一些香烟烟雾成分代谢的酶的基因中的五个多态性（CYP1A1、CYP1A2 和 NAT2）。使用逻辑回归模型分别估计母亲吸烟和母亲及婴儿基因变异的优势比（OR）和 95%置信区间（CI），并评估母亲吸烟和母亲或婴儿基因变异与腹裂的联合关联。在调整了母亲分娩时的年龄并按母亲种族-民族分层的分析中，我们在 30 个具有足够数量可计算 OR 的潜在关联中发现了三个提示关联：非西班牙裔白种母亲在围孕期吸烟的 CYP1A12A（aOR=0.38，95%CI 0.15-0.98），以及不吸烟的西班牙裔母亲及其婴儿的 NAT26（aOR=2.17，95%CI 1.12-4.19）和 2.11，95%CI 1.00-4.48）。这项分析不支持围孕期母亲吸烟与评估的大多数异生物质代谢酶基因变异之间发生效应修饰。
