Wang Xiaobin, Zuckerman Barry, Pearson Colleen, Kaufman Gary, Chen Changzhong, Wang Guoying, Niu Tianhua, Wise Paul H, Bauchner Howard, Xu Xiping
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, 91 E Concord St, Maternity 4, Boston, MA 02118, USA.
JAMA. 2002 Jan 9;287(2):195-202. doi: 10.1001/jama.287.2.195.
Little is known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcomes.
To investigate whether the association between maternal cigarette smoking and infant birth weight differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1.
DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 1998-2000 among 741 mothers (174 ever smokers and 567 never smokers) who delivered singleton live births at Boston Medical Center. A total of 207 cases were preterm or low-birth-weight infants and 534 were non-low-birth-weight, full-term infants (control).
Birth weight, gestation, fetal growth by smoking status and CYP1A1 MspI (AA vs Aa and aa, where Aa and aa were combined because of small numbers of aa and similar results), and GSTT1 (present vs absent) genotypes.
Without consideration of genotype, continuous maternal smoking during pregnancy was associated with a mean reduction of 377 g (SE, 89 g) in birth weight (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.7). When CYP1A1 genotype was considered, the estimated reduction in birth weight was 252 g (SE, 111 g) for the AA genotype group (n = 75; OR, 1.3; 95% CI, 0.6-2.6), but was 520 g (SE, 124 g) for the Aa/aa genotype group (n = 43 for Aa, n = 6 for aa; OR, 3.2; 95% CI, 1.6-6.4). When GSTT1 genotype was considered, the estimated reduction in birth weight was 285 g (SE, 99 g) (OR, 1.7; 95% CI, 0.9-3.2) and 642 g (SE, 154 g) (OR, 3.5; 95% CI, 1.5-8.3) for the present and absent genotype groups, respectively. When both CYP1A1 and GSTT1 genotypes were considered, the greatest reduction in birth weight was found among smoking mothers with the CYP1A1 Aa/aa and GSTT1 absent genotypes (-1285 g; SE, 234 g; P<.001). Among never smokers, genotype did not independently confer an adverse effect. A similar pattern emerged in analyses stratified by maternal ethnicity and in analyses for gestation.
In our study, maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, suggesting an interaction between metabolic genes and cigarette smoking.
关于香烟烟雾的遗传易感性与不良妊娠结局之间的关系，人们了解甚少。
研究母亲吸烟与婴儿出生体重之间的关联是否因两种母亲代谢基因（CYP1A1和GSTT1）的多态性而有所不同。
设计、地点和参与者：1998 - 2000年在波士顿医疗中心对741名单胎活产母亲（174名曾经吸烟者和567名从不吸烟者）进行的病例对照研究。共有207例为早产或低体重婴儿，534例为非低体重足月婴儿（对照）。
出生体重、孕周、根据吸烟状况以及CYP1A1 MspI（AA与Aa和aa，其中由于aa数量少且结果相似，将Aa和aa合并）和GSTT1（存在与不存在）基因型的胎儿生长情况。
不考虑基因型时，孕期母亲持续吸烟与出生体重平均降低377克（标准误，89克）相关（优势比[OR]，2.1；95%置信区间[CI]，1.2 - 3.7）。考虑CYP1A1基因型时，AA基因型组（n = 75；OR，1.3；95% CI，0.6 - 2.6）出生体重估计降低252克（标准误，111克），而Aa/aa基因型组（Aa组n = 43，aa组n = 6；OR，3.2；95% CI，1.6 - 6.4）出生体重降低520克（标准误，124克）。考虑GSTT1基因型时，基因型存在组和不存在组出生体重估计降低分别为285克（标准误，99克）（OR，1.7；95% CI，0.9 - 3.2）和642克（标准误，154克）（OR，3.5；95% CI，1.5 - 8.3）。同时考虑CYP1A1和GSTT1基因型时，出生体重降低最大的是CYP1A1 Aa/aa且GSTT1基因型不存在的吸烟母亲（-1285克；标准误，234克；P <.001）。在从不吸烟者中，基因型并未独立产生不良影响。按母亲种族分层的分析以及孕周分析中也出现了类似模式。
在我们的研究中，母亲的CYP1A1和GSTT1基因型改变了母亲吸烟与婴儿出生体重之间的关联，提示代谢基因与吸烟之间存在相互作用。
