Hou Ruiying, Ren Xiuyu, Wang Juan, Guan Xujun
Department of Pediatrics, Affiliated Hospital of Weifang Medical College, Weifang, Shandong, China.
Department of Obstetric, Affiliated Hospital of Weifang Medical College, Weifang, Shandong, China.
Mol Neurobiol. 2016 Dec;53(10):6653-6658. doi: 10.1007/s12035-015-9566-7. Epub 2015 Dec 8.
This study aims to examine whether the presence of polymorphisms in TNF-α (rs361525 and rs1799724) and MTHFR (rs1476413 and rs9651118) genes is associated with the pathogenesis of cerebral palsy (CP). A total of 105 CP patients and 114 age-, gender-, and ethnicity-matched healthy controls were genotyped for the selected polymorphisms, using TaqMan allelic discrimination assay. Odds ratios (OR) and 95 % confidence intervals (CI) were determined to measure the strength of associations of TNF-α and MTHFR polymorphisms with CP. The proportion of subjects with the gestational age more than 37 weeks or asphyxia was much larger in cases compared with controls (gestational age 63.8 vs. 34.2 %; asphyxia 25.7 vs. 7.9 %). The genotype frequencies of TNF-α rs1799724 were similar between groups (P > 0.05), yet the allele distributions were significantly different (P < 0.05). Both the allele and genotype distributions of MTHFR rs9651118 polymorphism varied significantly between the groups (P < 0.05). Subgroup analysis based on gestational age indicated a significant association between rs361525 and rs9651118 and CP with or without premature. TNF-α protein concentrations were significantly increased among patients with rs361525 GG genotype compared with controls. Also, a significant increase in the risk of CP was observed to be associated with the interactions of TNF-α rs1799724 and MTHFR rs9651118 (OR 2.75, 95 % CI 1.23-6.13). These data suggest that polymorphisms in TNF-α and MTHFR genes might be involved in the pathogenesis of CP in Chinese infants.
本研究旨在探讨肿瘤坏死因子-α(TNF-α,rs361525和rs1799724)及亚甲基四氢叶酸还原酶(MTHFR,rs1476413和rs9651118)基因多态性的存在是否与脑瘫(CP)的发病机制相关。采用TaqMan等位基因鉴别分析方法,对105例CP患者及114例年龄、性别和种族相匹配的健康对照者进行所选多态性的基因分型。计算比值比(OR)和95%置信区间(CI),以衡量TNF-α和MTHFR基因多态性与CP的关联强度。与对照组相比,病例组中孕周超过37周或有窒息史的受试者比例更高(孕周:63.8% 对34.2%;窒息:25.7% 对7.9%)。两组间TNF-α rs1799724的基因型频率相似(P>0.05),但等位基因分布存在显著差异(P<0.05)。MTHFR rs9651118多态性的等位基因和基因型分布在两组间均有显著差异(P<0.05)。基于孕周的亚组分析表明,rs361525和rs9651118与有无早产的CP均存在显著关联。与对照组相比,rs361525 GG基因型患者的TNF-α蛋白浓度显著升高。此外,观察到TNF-α rs1799724与MTHFR rs9651118的相互作用与CP风险显著增加相关(OR 2.75,95% CI 1.23 - 6.13)。这些数据表明,TNF-α和MTHFR基因多态性可能参与了中国婴儿CP的发病机制。