摘要
目的探讨神经连接蛋白-4(Neuroligin-4)基因多态性与中国汉族儿童孤独症的关系。方法选取Neuroligin-4基因上3'UTR区2个多态性位点rs3810687和rs3810688作为遗传标记,应用双脱氧链终止测序法对92个孤独症核心家系276名成员进行等位基因和基因型测定。对孤独症患儿及其父母分别进行Hardy-Weinberg平衡检验。在孤独症核心家系中应用单体型相对危险度分析(HRR)及传递不平衡检验(TDT)分析等位基因与孤独症的关系。结果 1.孤独症患儿及其父母观察值和预期值间差异均无统计学意义(Pa>0.05),研究对象均符合Hardy-Weinberg遗传平衡法则。2.在92个孤独症核心家系中,TDT检验显示rs3810687位点存在传递不平衡,C等位基因由杂合子父母传递给患病子代的频率高于A等位基因,差异有统计学意义(χ2=4.500,P=0.044);rs3810688位点2等位基因传递差异无统计学意义(χ2=0.362,P=0.630),由杂合子父母传递给患病子女的等位基因频率未偏离50%理论值。3.HRR分析结果与TDT检验结果一致:rs3810687位点存在传递不平衡,差异有统计学意义(χ2=12.556,P=0.000);rs3810688位点未见传递不平衡,差异无统计学意义(χ2=0.326,P=0.568)。结论 Neuroligin-4基因rs3810687位点与儿童孤独症相关,支持Neuroligin-4基因是孤独症的候选基因。
Objective To investigate the association between the Neuroligin -4 gene polymorphism and childhood autism in Chinese Han population. Methods Two SNPs （rs3810687 and rs3810688） of Neuroligin -4 gene 3＇untranslated region（3＇UTR） were chosen for ge- netic marker. Chain Termination Method was used to determine the allele and genotype of 276 members in 92 autism families. SNPs loci of children with autism and their parents were tested regarding Hardy - Weinberg equilibrium tests. The association between these two SNPs loci and autism were analyzed through haplotype relative risk （HRR） test and transmission disequilibrium test （TDT）. Results 1. The genotype distributions of the SNPs in autism children and their parents were consistent with the Hardy - Weinberg equilibrium （ Pa 〉 0.05 ）. 2. There was significant transmission disequilibrium in TDT （X^2 = 4. 500, P = 0. 044） for rs3810687 polymorphism. The rate of allele C transmitted from heterozygous parents to offspring was higher than that of transmitted A. While, there was no transmission disequilibrium for rs3810688 polymor- phism in TDT （X^2=0. 362 ,P =0. 630）. The transfer frequency of the allele from heterozygous parents to offspring was approximate 50%. 3. The result of HRR analysis was accordance with TDT. There was significant transmission disequilibrium for rs3810687 polymorphism （X^2=12. 556, P= 0. 000 ） in HRR test. While, no significant difference was found in rs3810688 polymorphism （X^2 = 0. 326, P = 0. 568 ）. Conclu- sions The polymorphism of rs3810687 in the Neuroligin - 4 gene is associated with childhood autism, Neuroligin - 4 gene is one of the candidate genes for autism.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2012年第7期526-528,共3页
Journal of Applied Clinical Pediatrics
基金
黑龙江省自然科学基金(D201045)
