van Beynum Ingrid M, Mooij Christiaan, Kapusta Livia, Heil Sandra, den Heijer Martin, Blom Henk J
Children's Heart Center, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Clin Chem Lab Med. 2008;46(10):1369-75. doi: 10.1515/CCLM.2008.271.
Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which plays a role in vasodilatation and in the regulation of cell growth and apoptosis. eNOS-deficient mice have impaired cardiac development resulting in congenital heart defects (CHDs). In humans, a single nucleotide polymorphism in the gene coding for eNOS (894G>T) is associated with birth defects.
We investigated the eNOS 894G>T polymorphism in relation to CHDs using a case-control study and a case-parent study. Possible interaction with maternal cigarette smoking during pregnancy and periconceptional folic acid supplementation was also investigated in a case-only approach.
The eNOS 894G>T polymorphism was genotyped in 170 CHD-affected children, in 161 of their mothers, 215 control children and 240 control women. For the case-parent study, 135 complete triads were available. The sum of eNOS 894 GT and TT vs. GG genotypes in children was associated with increased CHD risk [odds ratio, OR 1.5 (95% CI 1.03-2.31)]. There was no preferential transmission of the 894T allele [OR 1.2 (95% CI 0.81-1.69)]. Overall, the maternal eNOS 894 GT or TT vs. GG genotypes were not associated with increased CHD risk. The maternal 894TT genotype in combination with maternal smoking was associated with an increased risk, particularly for a subgroup of other than conotruncal heart defects [OR 3.3 (95% CI 1.00-11.1)]. No interaction with periconceptional folic acid supplementation was observed.
Our data indicate that the eNOS 894G>T polymorphism is associated with increased CHD risk. The study also provides evidence of a possible gene-environment interaction effect on CHD risk between the maternal eNOS 894G>T variant and maternal cigarette smoking during pregnancy. This observation should be interpreted with caution because of the relatively small subgroups. Further study in a larger group of CHD subjects is required.
内皮型一氧化氮合酶（eNOS）产生一氧化氮，其在血管舒张以及细胞生长和凋亡的调节中发挥作用。eNOS基因缺陷的小鼠心脏发育受损，导致先天性心脏病（CHD）。在人类中，编码eNOS的基因中的单核苷酸多态性（894G>T）与出生缺陷有关。
我们采用病例对照研究和病例-父母研究，调查了eNOS 894G>T多态性与CHD的关系。还采用仅病例研究方法，调查了孕期母亲吸烟和受孕前补充叶酸可能存在的相互作用。
对170名患CHD的儿童、161名儿童的母亲、215名对照儿童和240名对照女性进行了eNOS 894G>T多态性基因分型。对于病例-父母研究，有135个完整的三联体。儿童中eNOS 894 GT和TT与GG基因型之和与CHD风险增加相关[比值比，OR 1.5（95%可信区间1.03-2.31）]。894T等位基因没有优先传递[OR 1.2（95%可信区间0.81-1.69）]。总体而言，母亲的eNOS 894 GT或TT与GG基因型与CHD风险增加无关。母亲的894TT基因型与母亲吸烟相结合与风险增加相关，特别是对于除圆锥动脉干型心脏缺陷以外的一个亚组[OR 3.3（95%可信区间1.00-11.1）]。未观察到与受孕前补充叶酸的相互作用。
我们的数据表明，eNOS 894G>T多态性与CHD风险增加相关。该研究还提供了证据，表明母亲的eNOS 894G>T变异与孕期母亲吸烟之间可能存在基因-环境相互作用对CHD风险的影响。由于亚组相对较小，这一观察结果应谨慎解释。需要在更大的CHD受试者群体中进行进一步研究。
