中国汉族人群吲哚胺2,3-双加氧酶基因多态性与精神分裂症病例对照关联研究

A case-control study on the association of indoleamine 2,3-dioxygenase gene polymorphism with schizophrenia in Chinese Han population

目的探讨中国汉族人群中吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)基因单核苷酸多态性(single nucleotide polymorphisms,SNP)与精神分裂症的关联。方法采用病例对照研究方法,纳入2010年1月至2021年12月在新乡医学院第二附属医院住院的精神分裂症患者3700例(患者组),并于同期在新乡市及周边社区招募健康对照者8580名(对照组)。采集所有受试者空腹外周血并提取基因组DNA,采用基因芯片和突变扩增系统方法进行DNA基因分型。使用SHEsis在线软件分析IDO基因SNP基因型和等位基因频率,2组间差异比较采用卡方检验。通过Haploview v4.2软件进行连锁不平衡分析和单体型分析。采用多因子降维法分析SNP之间的相互作用。结果患者组和对照组IDO基因的4个SNP位点中,rs9657182位点的基因型和等位基因频率差异有统计学意义(χ^(2)=11.81,P=0.003;χ^(2)=5.54,P=0.019);经过Bonferroni校正后,rs9657182位点基因型差异仍具有统计学意义(P=0.011)。rs7820268、rs4503083和rs10109853的SNP位点的基因型和等位基因频率差异均无统计学意义。进一步按照男女性别分层,rs9657182位点的基因型频率2组性别差异无统计学意义。单体型分析显示由rs9657182和rs7820268组成的单体型CC和TC在2组间差异具有统计学意义(χ^(2)=3.93、4.78,P=0.048、0.029)。结论IDO基因rs9657182位点可能是精神分裂症的易感基因位点,单体型CC和TC可能与精神分裂症的发病相关。

ObjectivesTo investigate the association between single nucleotide polymorphisms(SNP)of indoleamine 2,3-dioxygenase(IDO)genes and schizophrenia(SZ)in a Chinese Han population.MethodsUsing a case-control study method,3700 in-patients with SZ were recruited from January 2010 to December 2021 at the Second Affiliated Hospital of Xinxiang Medical University,and 8580 healthy controls were recruited from surrounding communities in Xinxiang City.The patient group and control group were matched in gender and age.After collecting peripheral blood from all subjects and extracting genomic DNA,the sample DNA was genotyped using methods such as gene chips and amplification refractory mutation system.The association analysis between IDO gene SNPs and SZ was conducted using the online analysis tool SHEsis.The differences in IDO gene SNP genotype and allele frequency between the two groups were compared using chi-square test.Linkage disequilibrium analysis,haplotype analysis,and Hardy Weinberg equilibrium test were performed using Haploview v4.2 software.A multifactor dimensionality reduction software was used to evaluate the interaction between SNPs and SNP frequencies.ResultsIn the four SNP loci of IDO gene,there was a significant difference in genotype and allele frequency between the SZ patient and the health control at rs9657182 locus(χ^(2)=11.81,P=0.003;χ^(2)=5.54,P=0.019).After Bonferroni correction,the genotype difference at rs9657182 locus still showed statistical significance(P=0.011).There were no statistically significant differences in genotype and allele frequency among the three SNP locis(rs7820268,rs4503083,and rs10109853).Further stratified by gender,there was no significant difference in genotype frequency between the two groups at the rs9657182.Haplotype analysis revealed that the haplotype of CC and TC(rs9657182 and rs7820268)were significantly different between the two groups(χ^(2)=3.93,4.78,P=0.048,0.029).ConclusionThe rs9657182 locus of IDO gene may be a susceptible locus for SZ.The haplotype of CC and TC may be associated with the onset of SZ.