第6号染色体短臂HLA-Ⅱ区基因多态性与精神分裂症的关联性

Relationship between HLA class Ⅱ gene polymorphism and schizophrenia

目的:探讨人类第6号染色体短臂HLA-DRB1、DQB1、DQA2和DQB2基因多态性与中国北方汉族人群精神分裂症的关系。方法:采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)的方法对195例精神分裂症患者及其健康父母组成的核心家系的基因型进行检测,并利用遗传学统计方法进行传递不平衡检验(TDT)、单倍体相对风险(HRR)及单倍型分析。结果:病例组和对照组中基因型分布均符合Hardy-Weinberg平衡定律;HRR分析,DQA2基因的SNP(rs2239800:G/A碱基互换)等位基因频数在病例组和对照组中分布差异有显著性(2χ=5.021,P=0.025);TDT分析,杂合子父母双亲的2个不同等位基因传递概率没有偏离50%;单倍型分析,HLA-II区可能存在多个与精神分裂症相关联的易感位点。结论:DQA2基因rs2239800位点基因多态性与精神分裂症有关联。

Objective To investigate the genetic association of HLA class Ⅱ DRB1, DQB1, DQA2 and DQB2 locus with schizophrenia in the Han people of Northern China. Methods The polymerase chain reaction （PCR） and restrictive fragment length polymorphism （RELP） were applied to detect the gene types in the 195 Han family trios including patients with schizophrenia and their healthy parents in the north of China. The chi-square （X^2） test, transmission disequilibrium test （TDT） and the haplotype relative risk （HRR） analysis were used to process the genotyping data statistically. Results The genotypic frequency of four genes did not deviate from Hardy-Weinberg equilibrium in both case and control groups; The SNP rs2239800, a G to A base change, presented in the DQA2 locus. Its allelic frequencies showed significant difference between case and control （X62 = 5. 021, P= 0. 025）. And the AA genotype of rs2239800 showed associations with schizophrenia. Conclusion The polymorphism of rs2239800 in the DQA2 gene may be associated with schizophrenia.