六号染色体短臂MHC区DRB3、DRB1基因多态性与精神分裂症症状的关系探讨

目的 探讨六号染色体短臂MHC区DRB3、DRBl基因多态性与精神分裂症症状的相关性。方法 采用聚合酶链反应(PCR)和限制性内切酶片段长度多态性(RFLP)方法检测两个基因位点上的单核苷酸多态性(SNPs)，并对116例精神分裂症患者家系进行连锁不平衡分析。结果 DRBl的SNP(rs707954：G／T碱基互换)等位基因与关系妄想症状呈显著相关(X^2=5．484，df=l，P=0．019)，GG、GT、TT三种基因型频率在关系妄想症状中呈显著相关(X^2=6．771，df=2，P=0．034)。rs707954的三种基因型频率与情感淡漠症状呈显著相关(X^2=12．110，df=4，P=0．017)。结论 DRBl位点等位基因与关系妄想和情感淡漠症状高度相关，DRBl基因型与关系妄想症状高度相关。

Study on the genetic association between DRB3 and DRB1 loci in the human MHC region and psychotic symptoms of schizophrenia

OBJECTIVE: The genomic region of the human major histocompatibility complex (MHC) is located in the short arm of chromosome 6 (6p). Linkage studies have shown that the 6p region may contain a gene for schizophrenia, the MHC region has thus become particularly important in searching for the schizophrenia susceptibility gene. The present study was designed to investigate the genetic association of DRB3 and DRB1 genes with psychotic symptoms of schizophrenia. METHODS: PCR-based restriction fragment length polymorphism (RFLP) analysis was applied to genotype two single nucleotide polymorphisms (SNPs) located in the DRB3 locus and in the DRB1 one in 116 Chinese Han family trios consisting of fathers, mothers and affected offspring with schizophrenia. Chi-square (chi(2)) test and haplotype-based relative risk (HRR) analysis were used on genotyping data. RESULTS: Data on HRR analysis did not show a genetic association either between the DRB3 locus and schizophrenia or between the DRB1 locus and the illness. However, the SNP rs707954, a G to T base change, present in the DRB1 locus showed strong association with idea of reference (chi(2) = 5.484, df = 1, P = 0.019), while the genotype of rs707954 showed an association with idea of reference (chi(2) = 6.771, df = 2, P = 0.034) as will as with apathy (chi(2) = 12.110, df = 4, P = 0.017). CONCLUSION: DRB1 locus seemed likely to be associated with psychotic symptoms as idea of reference and apathy. Further studies were necessary to reveal the relations between DRB1 gene or nearby locus with its susceptibility to schizophrenia.