中国汉族人群TSC1、TSC2和PTEN基因多态性和孤独症的关联研究

Association study between polymorphisms of TSC1, TSC2 ,PTEN genes and autism in Chinese Han population

目的 探讨中国汉族人群TS C1、TSC2和PTEN基因与孤独症间的相关性.方法 选取TS C1、TSC2和PTEN基因的13个标签SNPs,即rs739441、rs2809244、rs 1050700、rs3761840、rs2074968、rs8063461、rs2074969、rs2072314、rs17562384、rs532678、rs17107001、rs12569998、rs2299941,使用SNaPshot基因分型技术进行分型,以274例孤独症患者和386名健康对照为研究对象,使用SHEsis分析软件比较两组间的等位基因和单体型分布频率有无差异,使用SNPStats分析软件比较两组间的基因型分布频率有无差异.结果 经Bonferroni校正后,rs2809244（TSCI）（x2=9.537,P=0.002,校正后P=0.016）、rs1050700（TSC1）（x2=9.313,P=0.002,校正后P=0.016）、rs2072314（TSC2）（x2=30.925,P＜0.01,校正后P＜0.01）和rs8063461（TSC2）（x2=57.784,P＜0.01,校正后P＜0.01）的等位基因频率在两组间差异有统计学意义（P＜0.05）;rs2072314（TSC2）（P＜0.01,校正后P＜0.01）、rs8063461（TSC2）（P＜0.01,校正后P＜0.01）的基因型频率在两组间差异有统计学意义（P＜0.05）.单体型分析中,单体型区块rs2809244-rs3761840构建的单体型A-G（OR=14.548,95％ CI=5.450～ 38.830）在两组间的分布频率差异有统计学意义（P＜0.05）,能够增加孤独症的发生风险;rs2074969-rs8063461构建的单体型A-A（OR=0.608,95％ CI =0.409～0.903,P=0.013）、G-A（OR=7.812,95％ CI =5.338～ 11.459,P＜0.01）及G-G（OR=0.356,95％ CI =0.274～0.463,P＜0.01）的分布频率在两组间差异有统计学意义（P＜0.05）,其中A-A、G-G能够降低孤独症的发生风险,而G-A能够增加孤独症的发生风险.结论 在中国汉族人群中,TSC1和TSC2基因可能与孤独症存在一定相关性.

Objective To explore the association between the polymorphisms of TSC1,TSC2,PTEN genes and autism in Chinese Han population.Methods 274 autism patients and 386 heahh controls were recruited,and SnaPshot technique was used to genotype the 13 tagSNPs of TSC1,TSC2 and PTEN genes.The allele,genotype and haplotype frequencies of the SNPs were compared using SHEsis and SNPStats softwares.Results Mter Bonferroni correction,the allele distribution of rs2809244 （TSC1） （x2 =9.537,P=0.002,adjusted P=0.016）,rs1050700 （TSC1） （x2 =9.313,P=0.002,adjusted P=0.016）,rs2072314（TSC2） （P〈0.01,adjusted P〈0.01） and rs8063461 （TSC2） （P〈0.01,adjusted P〈0.01）showed significant difference between two groups （P〈0.05）.The genotype frequencies of rs2072314（TSC2）and rs8063461（TSC2） showed significant difference between two groups（P〈0.05）.Moreover,the frequency of haplotype A-G （OR =14.548,95% CI =5.450-38.830） in the haplotype block rs2809244-rs3761840 showed significant difference between two groups（P〈0.05）,A-G significantly increases the risk of autism.The frequencies of haplotype A-A （OR=0.608,95% CI =0.409-0.903,P=0.013）,G-A （OR=7.812,95% CI =5.338-11.459,P〈0.01）and G-G （OR=0.356,95% CI =0.274-0.463,P〈0.01） in the haplotype block rs2074969-rs8063461 were identified,which were significant difference between two groups（P〈0.05）,and AA and G-G significantly reduced but G-A increased the risk of autism.Conclusion The polymorphisms of TSC1 and TSC2 genes might associate with autism in Chinese Han population.