TSC1、TSC2基因多态性和儿童孤独症的家系研究  

Family-based association study of the TSC1,TSC2 genes polymorphisms in children with autism

作　　者：刘漪[1] 张燕霞 禹顺英[1] 杜亚松[1] 

机构地区：[1]上海交通大学医学院附属精神卫生中心,上海200030

出　　处：《中国儿童保健杂志》2013年第6期571-574,共4页Chinese Journal of Child Health Care

基　　金：国家重点基础研究发展计划(973)(2010CB529602);上海市科委重点项目(11411952401);上海市新三年计划项目(GWIII-32)

摘　　要：【目的】探讨结节性硬化症(tuberous sclerosis complex,TSC)相关基因TSC1、TSC2基因多态性与儿童孤独症之间的关联。【方法】利用SNaPshot基因分型技术,在97例孤独症核心家系中,对TSC1、TSC2基因上的8个标签SNP,即rs3761840、rs2809244、rs1050700、rs739441、rs2074968、rs2074969、rs2072314、rs8063461进行分型;通过FBAT软件及Haploview软件进行基于家系的单倍型分析。【结果】1)基于家系的关联分析发现8个SNPs等位基因中有2个SNPs的等位基因倾向于过传递(rs1050700A:Z=2.708,P=0.006769;rs2074968G:Z=3.244,P=0.001180),并且经过FDR校正后,2个SNPs仍显示出与孤独症之间存在显著关联性(校正P值分别为0.027,0.014)。2)rs3761840-rs2809244基因型的单体型A-C显示出显著的传递不平衡,双亲较少传递给子女(Z=-2.297,P=0.021629)。rs2074968-rs2072314基因型的2种单体型即G-C及C-C均显示出显著的传递不平衡,单体型G-C能从双亲过传递给子女(Z=2.596,P=0.009444),单体型C-C则相反(Z=-3.657,P=0.000256)。【结论】TSC1、TSC2基因可能与儿童孤独症的发生存在关联。[Objective] To explore the characteristics of TSC1 and TSC2 genes polymorphisms in children with autism. [Methods] Eight tag single nucleotide polymorphisms （SNPs） were genotyped inTSC1 and TSC2 genes, from 97 autistic trios using SNaPshot technique. Single SNP haplotype association analysis were performed using the family-based association test （FBAT） and Haploview software. [Resluts] 1）In a family-based association test,two SNPs showed significant associations with autism （rs1050700 A..Z=2. 708,P=0. 006769;rs2074968 G：Z=3. 244,P=0. 001180）. After the FDR correction, they all remained significant. 2） Haplotype association analysis showed that three haplotypes, G-C （rs2074968-rs2072314） ,A-C（rs3761840-rs2809244） ,C-C（rs2074968-rs2072314）displayed the significant associations with autism. [Conclusions] The SNPs of TSC1 and TSC2 genes might be the susceptive genes in autism. It suggested that these genes polymorphisms might play the important roles in the pathogenesis of autism.

关 键 词：孤独症 TSC1 TSC2 DNA测序 

分 类 号：R749.94[医药卫生—神经病学与精神病学]