Lu Xiaolin, Wang Zhen, Wang Jianhua, Shangguan Shaofang, Bao Yihua, Lu Ping, Wang Li
Capital Institute of Pediatrics, Beijing, China.
Int J Neurosci. 2014 Jun;124(6):436-42. doi: 10.3109/00207454.2013.849249. Epub 2013 Nov 7.
Neural tube defects (NTDs) in mammals are rooted in aberrant neural tube closure during early embryogenesis, which is caused by multiple environmental and genetic factors. The Sonic Hedgehog pathway is involved in the induction of the floor plate and participates in formation of the neural tube. Mutation of the suppressor of fused gene (SUFU), an essential repressor of Sonic Hedgehog signaling pathway, can result in NTDs. A case-control study was designed to compare the frequencies of the polymorphism at four sites in the SUFU gene in control and NTDs group, as well as in subtype groups, including anencephaly, spina bifida and encephalocele. We also explored the association between polymorphism and NTDs risk in a high prevalence population in China. Rs10786691, but not the other three SNPs, had an association between polymorphisms and NTDs. The heterozygous AG allele of rs10786691 was significantly related with NTDs and encephalocele (OR = 1.60, 95% CI: 1.04-2.48, p = 0.034; OR = 2.83, 95% CI: 1.07-7.47, p = 0.036). In female but not male fetuses, the AG genotype of rs10786691 increased the risk of NTDs (OR = 1.88, 95% CI: 1.03-3.41, p = 0.040). The SUFU rs10786691 A>G polymorphism may be a potential risk factor for NTDs and encephalocele in this high-risk population, but the association between the polymorphism and NTDs was probably influenced by gender.
哺乳动物的神经管缺陷(NTDs)源于胚胎早期发育过程中神经管闭合异常,这是由多种环境和遗传因素引起的。音猬因子(Sonic Hedgehog)信号通路参与底板的诱导并参与神经管的形成。融合基因抑制因子(SUFU)是音猬因子信号通路的重要抑制因子,其突变可导致神经管缺陷。本病例对照研究旨在比较对照组与神经管缺陷组以及包括无脑儿、脊柱裂和脑膨出在内的亚型组中SUFU基因四个位点的多态性频率。我们还在中国一个高患病率人群中探讨了多态性与神经管缺陷风险之间的关联。rs10786691(而非其他三个单核苷酸多态性)的多态性与神经管缺陷之间存在关联。rs10786691的杂合AG等位基因与神经管缺陷和脑膨出显著相关(比值比[OR]=1.60,95%置信区间[CI]:1.04 - 2.48,p = 0.034;OR = 2.83,95% CI:1.07 - 7.47,p = 0.036)。在女性胎儿而非男性胎儿中,rs10786691的AG基因型增加了神经管缺陷的风险(OR = 1.88,95% CI:1.03 - 3.41,p = 0.040)。在这个高风险人群中,SUFU基因rs10786691 A>G多态性可能是神经管缺陷和脑膨出的潜在风险因素,但该多态性与神经管缺陷之间的关联可能受性别影响。