【摘要】 目的 探讨人白细胞抗原-G(HLA-G)基因多态性与精神分裂症(SCZ)遗传易感性的相关性。方法 选择2015年9月至2017年5月新乡医学院第二附属医院收治的SCZ患者353例为SCZ组，另选择同期健康体检者362例作为对照组。采用聚合酶链式反应和Sanger测序技术对2组受试者的HLA-G基因外显子2、4、8进行基因分型，比较2组受试者的等位基因、基因型和单倍型的差异性，并分析在不同遗传模式下HLA-G单核苷酸多态性(SNP)与SCZ易感性的相关性。结果 从HLA-G基因外显子2、4、8共检测到7个SNP位点，除rs9258495 (+324G/T)外，其余6个SNP位点的基因型分布均符合Hardy-Weinberg平衡。SCZ组和对照组受试者7个HLA-G SNP位点基因型频率比较差异均无统计学意义(P>0.05)。SCZ组患者rs1628628(+188C/T)的T等位基因频率显著高于对照组(P<0.05);其余各等位基因频率2组间比较差异均无统计学意义(P>0.05)。rs1628628(+188C/T)的T等位基因通过不同遗传模式(加性模型、显性模型、共显性模型)增加SCZ的发病风险(P<0.05)。连锁不平衡(LD)和单倍型分析结果显示，rs1628628和rs1130355之间有相对较强的LD(D′=0.943,r~2=0.612)。SCZ组与对照组受试者单倍型CAGCAI和TAGCAD的分布频率比较差异有统计学意义(P<0.05)。单倍型TAGCAD显著增加SCZ的发病风险(P<0.05),而单倍型CAGCAI可显著降低SCZ的发病风险(P<0.05)。结论 HLA-G的rs1628628位点多态性可能与SCZ的遗传易感性相关，单倍型TAGCAD可增加人群SCZ遗传易感风险。更多还原

【Abstract】 Objective To investigate the association between human leukocyte antigen-G(HLA-G) gene polymorphism and the genetic susceptibility of schizophrenia(SCZ).Methods Three hundred and fifty-three SCZ patients in the Second Affiliated Hospital of Xinxiang Medical University from September 2015 to May 2017 were selected as the SCZ group, and 362 healthy subjects in the same period were selected as the control group.HLA-G gene exons 2,4,and 8 of all subjects were genotyped by polymerase chain reaction and Sanger sequencing.The difference of alleles, genotypes and haplotypes was compared between the two groups, and the association between the HLA-G single nucleotide polymorphism(SNP) and the susceptibility of SCZ was analyzed under different genetic patterns.Results Seven SNP sites were detected from exons 2,4 and 8 of the HLA-G gene.Except for rs9258495(+324 G/T),the genotype distribution of the other 6 SNP sites accorded with Hardy-Weinberg equilibrium.There was no significant difference in the genotype frequency of 7 HLA-G SNP sits between the SCZ group and the control group(P>0.05).The T allele frequency of rs1628628(+188 C/T)of patients in the SCZ group was significantly higher than that in the control group(P<0.05);there was no significant difference in the frequency of another alleles between the two groups(P>0.05).The T allele of rs1628628(+188 C/T) increased the risk of SCZ through different genetic models(additive model, dominant model and co-dominant model).Linkage disequilibrium(LD) and haplotype analysis result showed that there was a relatively strong LD between rs1628628 and rs1130355(D′=0.943,r~2=0.612).There was a significant difference in the distribution frequency of haplotype CAGCAI and TAGCAD between the SCZ group and the control group(P<0.05).The haplotype TAGCAD significantly increased the risk of SCZ(P<0.05),while the haplotype CAGCAI significantly decreased the risk of SCZ(P<0.05).Conclusion HLA-G rs1628628 polymorphism may be associated with the genetic susceptibility of SCZ,and the haplotype TAGCAD can increase the susceptibility risk of SCZ.更多还原