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【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 investigate the association between TSC1, TSC2 gene polymorphism and childhood autism in tuberous sclerosis complex (TSC). 【Method】 Eight SNPs of TSC1 and TSC2 genes, ie rs3761840, rs2809244, rs1050700, rs739441, rs2074968, rs2074969, rs2072314 and rs8063461, were genotyped in 97 autistic nuclear families using SNaPshot genotyping ; Family-based haplotype analysis with FBAT software and Haploview software. 【Results】 1) Based on pedigree association analysis, it was found that alleles of 2 of 8 SNPs tended to be overexpressed (rs1050700A: Z = 2.708, P = 0.006769; rs2074968G: Z = 3.244, P = 0.001180 ), And after the FDR correction, the two SNPs still showed a significant association with autism (adjusted P values were 0.027,0.014, respectively). 2) The haplotypes A-C of the rs3761840-rs2809244 genotype showed a significant imbalance of transmission, with less transmission of the parents to their children (Z = -2.297, P = 0.021629). Two haplotypes, GC and CC, of rs2074968-rs2072314 genotype showed significant transmission imbalance. The haplotype GC was able to pass from parents to children (Z = 2.596, P = 0.009444) In contrast (Z = -3.657, P = 0.000256). 【Conclusion】 TSC1 and TSC2 genes may be associated with autism in children.