Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China (mainland).
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China (mainland).
Med Sci Monit. 2018 Jul 19;24:5015-5026. doi: 10.12659/MSM.907492.
BACKGROUND DNA Base Excision Repair Gene-DNA LigaseIII (LIG3) is an important repair gene in the repair pathway and plays an important role in maintaining the integrity of mitochondria. Rs1052536 and rs3135967 polymorphisms of the gene are associated with lung cancer, keratoconus, and Fuchs endothelial corneal dystrophy. There is no previously published report on the relationship between the polymorphisms and neural tube defects (NTDs). MATERIAL AND METHODS Mass ARRAY iPLEX was used to determine the distribution of the polymorphisms in the case group of 108 NTD pregnant women and a control group of 233 normal healthy pregnant women to examine the relevance of their polymorphisms and NTD occurrence. RESULTS The homozygotes of rs1052536 TT were associated with an increased risk for NTDs than CC (P=0.014, OR=2.31, 95%CI [1.17-4.54]), and variants of rs1052536 T were associated with an increased risk of NTDs (P=0.024, OR=1.50, 95%CI [1.06-2.13]). The stratified analysis showed that TT genotype of rs1052536 increased the risk of anencephaly (P=0.016, OR=2.69, 95%CI [1.18-6.10]) and the T allele significantly increased the risk of cranial NTDs (P=0.033, OR=1.56, 95%CI [1.04-2.35]). CONCLUSIONS Rs1052536 in LIG3 gene might be a potential genetic risk factor in a high-risk area of NTDs in China.
DNA 碱基切除修复基因- DNA 连接酶 III(LIG3)是修复途径中的一个重要修复基因,在维持线粒体完整性方面发挥着重要作用。该基因的 rs1052536 和 rs3135967 多态性与肺癌、圆锥角膜和 Fuchs 内皮角膜营养不良有关。目前还没有关于这些多态性与神经管缺陷(NTDs)之间关系的报道。
采用 Mass ARRAY iPLEX 技术检测了 108 例 NTD 孕妇病例组和 233 例正常健康孕妇对照组中基因多态性的分布情况,以检验其多态性与 NTD 发生的相关性。
rs1052536 的 TT 纯合子与 NTD 的发生风险高于 CC(P=0.014,OR=2.31,95%CI [1.17-4.54]),rs1052536 的 T 变异型与 NTD 的发生风险相关(P=0.024,OR=1.50,95%CI [1.06-2.13])。分层分析显示,rs1052536 的 TT 基因型增加了无脑畸形的风险(P=0.016,OR=2.69,95%CI [1.18-6.10]),T 等位基因显著增加了颅 NTD 的风险(P=0.033,OR=1.56,95%CI [1.04-2.35])。
LIG3 基因中的 rs1052536 可能是中国 NTD 高危地区的一个潜在遗传危险因素。