小儿脑性瘫痪与ATG5多态性的关联性及危险因素分析

Association of ATG5 polymorphisms with cerebral palsy in children and analysis of risk factors

目的分析自噬相关基因5(ATG5)多态性与小儿脑性瘫痪(CP)的关联性,探究影响CP发生的危险因素。方法选择2022年1月—2024年1月我院收治的118例CP患儿为研究对象,纳入研究组;选择同期收治的200例非CP小儿纳入对照组。应用聚合酶链式反应-限制性酶切片段长度多态性(PCR-RFLP)技术检测ATG5基因单核苷酸多态性(SNP)位点rs510432、rs573775、rs2299863、rs3804338、rs6568431多态性,采用酶联免疫吸附试验(ELISA)法检测2组儿童血浆ATG5水平,采用logistic回归分析ATG5基因多态性与小儿CP易感性的关系。结果研究组和对照组ATG5基因rs6568431位点AA、AC、CC基因型频率分别为25.42%、40.68%、33.90%和8.00%、40.00%、52.00%,差异有统计学意义(P<0.05),2组儿童rs510432、rs573775、rs2299863、rs3804338位点各基因型频率比较,差异均无统计学意义(P>0.05)。研究组和对照组儿童ATG5基因rs6568431位点A、C等位基因频率分别为45.76%、54.24%和28.00%、72.00%,差异有统计学意义(P<0.05),rs510432、rs573775、rs2299863、rs3804338位点各等位基因频率比较,差异均无统计学意义(P>0.05)。研究组儿童血浆ATG5水平为(8.42±0.95)ng/mL,明显低于对照组的(10.67±0.99)ng/mL,差异有统计学意义(t=19.872,P<0.05),且携带AA基因型儿童的血浆ATG5水平明显低于携带AC+CC基因型儿童,差异有统计学意义(P<0.05)。单因素分析结果显示,2组儿童母亲既往不良孕产史、母亲妊娠期高血压、母亲孕期羊水异常、宫内窘迫、病理性黄疸以及缺血缺氧性脑病情况的差异均有统计学意义(P<0.05)。多因素logistic回归分析结果显示,母亲有既往不良孕产史、母亲孕期羊水异常、宫内窘迫、病理性黄疸、缺血缺氧性脑病以及ATG5基因rs6568431位点多态性是CP发生的影响因素,差异均有统计学意义(P<0.05)。结论ATG5基因rs6568431位点多态性与小儿CP易感性存在关联性,且携带AA基因型可能增加小儿CP发生风险。此外,小儿CP的发生还与母亲既往不良孕产史、母亲孕期羊水异常、宫内窘迫、病理性黄疸以及缺血缺氧性脑病等多种因素有关,故针对高危因素进行积极预防,有助于减少小儿CP的发生。

Objective To analyze the association of autophagy-related gene 5(ATG5)polymorphisms with cerebral palsy(CP)in children and to explore the risk factors influencing the occurrence of CP.Methods A total of 118 children with CP admitted to our hospital from January 2022 to January 2024 were selected as the study group;200 non-CP children admitted during the same period were included as the control group.The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique was used to detect the single nucleotide polymorphisms(SNPs)of the ATG5 gene at positions rs510432,rs573775,rs2299863,rs3804338,and rs6568431.Enzyme-linked immunosorbent assay(ELISA)was used to measure the plasma ATG5 levels in both groups of children,and logistic regression analysis was conducted to assess the relationship between ATG5 gene polymorphisms and the susceptibility to CP in children.Results The genotype frequencies of the ATG5 gene rs6568431 site AA,AC,and CC in the study and control groups were 25.42%,40.68%,33.90%,and 8.00%,40.00%,52.00%,respectively,with a statistically significant difference(P<0.05).The genotype frequencies at the rs510432,rs573775,rs2299863,and rs3804338 sites showed no statistically significant differences between the two groups(P>0.05).The allele frequencies of the A and C alleles at the rs6568431 site in the study and control groups were 45.76%,54.24%,and 28.00%,72.00%,respectively,with a statistically significant difference(P<0.05).The allele frequencies at the rs510432,rs573775,rs2299863,and rs3804338 sites showed no statistically significant differences(P>0.05).The plasma ATG5 level in the study group was(8.42±0.95)ng/mL,which was significantly lower than that in the control group(10.67±0.99)ng/mL,with a statistically significant difference(t=19.872,P<0.05).Children with the AA genotype had significantly lower plasma ATG5 levels than those with the AC+CC genotype,with a statistically significant difference(P<0.05).Univariate analysis results showed that the differences in the history of adverse obstetric history,maternal hypertension during pregnancy,abnormal amniotic fluid during pregnancy,fetal distress,pathological jaundice,and hypoxic-ischemic encephalopathy between the two groups were statistically significant(P<0.05).Multivariate logistic regression analysis results showed that a history of adverse obstetric history,abnormal amniotic fluid during pregnancy,fetal distress,pathological jaundice,hypoxic-ischemic encephalopathy,and the rs6568431 polymorphism of the ATG5 gene were risk factors for the occurrence of CP,with statistically significant differences(P<0.05).Conclusion The polymorphism at the rs6568431 site of the ATG5 gene is associated with susceptibility to CP in children,and carrying the AA genotype may increase the risk of CP in children.In addition,the occurrence of CP in children is also correlated with various factors such as a history of adverse obstetric history,abnormal amniotic fluid during pregnancy,fetal distress,pathological jaundice,and hypoxic-ischemic encephalopathy.Therefore,active prevention of high-risk factors can help reduce the occurrence of CP in children.