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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 relationship between Neuroligin-4 gene polymorphism and autism in Chinese Han children. Methods Two polymorphic sites rs3810687 and rs3810688 in the 3’UTR region of Neuroligin-4 gene were selected as genetic markers. The allele and genotypes of 276 members of 92 autism nuclear families were determined by dideoxy chain termination sequencing . Children with autism and their parents were Hardy-Weinberg balance test. The relationship between autism and autism was analyzed by haplotype relative risk analysis (HRR) and transmission disequilibrium test (TDT) in the nuclear family of autism. Results 1. There was no significant difference between the children with autism and their parents’ observation and the expected value (Pa> 0.05). All the subjects were in accordance with the Hardy-Weinberg genetic balance rule. In 92 autism nuclear pedigrees, the TDT test showed that the rs3810687 locus was imbalanced, and the frequency of the C allele passed from heterozygotic parents to affected children was higher than that of allele A, the difference was statistically significant (χ2 = 4.500, P = 0.044). There was no significant difference in the allele frequencies of rs3810688 between the two groups (χ2 = 0.362, P = 0.630) % Theoretical value. The results of HRR analysis were consistent with the results of TDT test. Rs3810687 site was imbalanced, the difference was statistically significant (χ2 = 12.556, P = 0.000); rs3810688 site showed no imbalance of transmission, the difference was not statistically significant (χ2 = = 0.326, P = 0.568). Conclusion The rs3810687 locus of Neuroligin-4 gene is associated with autism in children and supports Neuroligin-4 gene as a candidate gene for autism.