精神分裂症断裂点基因1单核苷酸多态性与中国汉族儿童孤独症的关系

Association study of disrupted in schizophrenia 1 gene polymorphisms with autism in Chinese Han children

目的探讨精神分裂症断裂点基因1（DISCl）单核苷酸多态性（SNPs）与中国汉族儿童孤独症的关系。方法采用ⅢuminaHumanHapCNV370-Duo芯片对278个孤独症核心家系（患儿及其父母）、157例孤独症患儿和435例正常对照进行全基因组SNP分型。从中选取DISCl基因的分型数据，采用病例一对照关联分析及传递不平衡检验分析等位基因与孤独症的关系。结果共有52个SNPs纳入本研究。1．病例一对照关联分析结果发现，6个位点（rs4658939，rs2793093，rsl0495309，rs2492367，rs11122362，rsl073179）的等位基因频率，以及7个单体型（rs823163-rs823161-rs4658933-rsl417585-rsl0864693-rs6541281构建的单体型AGAAAG，rs4658939一rs2793093一rs10495309构建的单体型GGG和AAA，rs2492367-rsl2046794构建的单体型GG和AG，rs9432040-rs2356606-rs11122362构建的单体型GAA，rs9431714-rsl073179构建的单体型GG）的频率在孤独症组和对照组间的差异均有统计学意义（矿=4．704、4．915、5．568、8．087、4．043、5．183、5．369、5．295、4．440、5．304，7．615、4．018，4．811，P=0．030、0．027、0．018、0．005、0．044、0．023、0．021、0．021、0．035、0j021、0．006、0．045、0．028）。2．传递不平衡检验分析表明，rs4658945位点的等位基因A和rslll22362位点的等位基因G，以及rsl0495310-rs4658945构建的单体型AG和rs9432040-rs2356606-rs11122362构建的单体型GAA在亲代与受累子代间的传递差异有统计学意义X2=4．445、5．400、3．973、5．126，P=0．035、0．020、0．046、0．024）。结论DISC1基因rs11122362位点及rs9432040-rs2356606．rs11122362构建的单体型GAA与孤独症存在关联，支持DISC1基因与中国汉族儿童孤独症的易感性相关。

Objective To investigate the relationship between the single nucleotide polymorphisms（SNPs） of disrupted in schizophrenia 1 （ DISC1 ） gene and autism in Chinese Han children. Methods Genome-wide SNP genoty- ping was performed by using Illumina HumanHap CNV370-Duo Chip in 278 autistic trios, 157 autistic individuals and 435 healthy controls. Genotype data of SNPs within DISC1 gene were selected. The association between these SNPs loci and autism was analyzed through case-control association analysis and family-based transmission disequilibrium test. Results Fifty-two SNPs were involved for further analysis. 1. Case-control association analysis showed that 6 SNPs （ rs4658939, rs2793093, rs10495309, rs2492367, rsl 1122362, rs1073179 ） and 7 haplotypes （ AGAAAG constructed with rs823163-rs823161-rs4658933-rs1417585-rs10864693-rs6541281, GGG and AAA constructed with rs4658939- rs2793093-rs10495309, GG and AG constructed with rs2492367-rs12046794, GAA constructed with rs9432040- rs2356606 -rs 11122362 and GG constructed with rs9431714-rs 1073179） had significant differences between autistic pa- tients and controls（x2 =4. 704,4. 915,5. 568,8. 087,4. 043,5. 183,5. 369,5. 295,4. 440,5. 304,7. 615,4. 018, 4. 811 ,P =0.030,0.027,0.018,0.005,0.044,0. 023,0. 021,0.021,0.035,0. 021,0. 006,0. 045,0.028）. 2. In the transmission disequilibrium test analysis, 2 SNPs （ rs4658945, rsl 1122362 ） and 2 haplotypes （ AG constructed with rs10495310-rs4658945, GAA constructed with rs9432040-rs2356606-rsll122362 ） showed significant transmission disequilibrium（x2 = 4. 445,5.400,3. 973,5. 126 ,P = 0. 035,0.020,0.046,0. 024 ）. Conclusions The polymorphism of rsl 1122362 and GAA haplotype constructed with rs9432040-rs2356606-rsl1122362 are associated with autism, and DISC1 gene is a susceptibility gene for autism in Chinese Han children.