van der Linden Ivon J M, Heil Sandra G, den Heijer Martin, Blom Henk J
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Department of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
J Hum Genet. 2007;52(6):516-520. doi: 10.1007/s10038-007-0147-0. Epub 2007 May 4.
The 894G>T single nucleotide polymorphism (SNP) in the endothelial NOS (NOS3) gene, has recently been associated with embryonic spina bifida risk. In this study, a possible association between the NOS3 894G>T SNP and spina bifida risk in both mothers and children in a Dutch population was examined using both a case-control design and a transmission disequilibrium test (TDT). Possible interactions between the NOS3 894G>T SNP and the MTHFR 677C>T SNP, elevated plasma homocysteine, and decreased plasma folate concentrations were also studied. The NOS3 894TT genotype did not increase spina bifida risk in mothers or children (OR 1.50, 95%CI 0.71-3.19 and OR 1.78, 95%CI 0.75-4.25, respectively). The TDT demonstrated no preferential transmission of the NOS3 894T allele (Chi2=0.06, P=0.81). In combination with the MTHFR 677TT genotype or elevated plasma homocysteine concentrations, the NOS3 894GT/TT genotype increased maternal spina bifida risk (OR 4.52, 95%CI 1.55-13.22 and OR 3.38, 95%CI 1.46-7.84, respectively). In our study population, the NOS3 894GT/TT genotype might be a risk factor for having a spina bifida affected child in mothers who already have an impaired homocysteine metabolism.
内皮型一氧化氮合酶（NOS3）基因中的894G>T单核苷酸多态性（SNP），最近被发现与胚胎脊柱裂风险相关。在本研究中，采用病例对照设计和传递不平衡检验（TDT），研究了荷兰人群中NOS3 894G>T SNP与母亲和儿童脊柱裂风险之间的可能关联。还研究了NOS3 894G>T SNP与MTHFR 677C>T SNP、血浆同型半胱氨酸升高和血浆叶酸浓度降低之间的可能相互作用。NOS3 894TT基因型并未增加母亲或儿童患脊柱裂的风险（比值比分别为1.50，95%可信区间0.71 - 3.19和1.78，95%可信区间0.75 - 4.25）。TDT显示NOS3 894T等位基因无优先传递（卡方=0.06，P = 0.81）。与MTHFR 677TT基因型或血浆同型半胱氨酸浓度升高相结合时，NOS3 894GT/TT基因型增加了母亲患脊柱裂的风险（比值比分别为4.52，95%可信区间1.55 - 13.22和3.38，95%可信区间1.46 - 7.84）。在我们的研究人群中，对于同型半胱氨酸代谢已受损的母亲，NOS3 894GT/TT基因型可能是生育脊柱裂患儿的一个风险因素。
