一氧化氮合酶1、神经细胞PAS域蛋白4和外中心粒物质1基因型与偏执型精神分裂症表型的关联性

Association study of nitric oxide synthase 1,neuronal PAS domain protein 4 and pericentriolar material 1 gene polymorphisms with the phenotype of paranoid schizophrenia

目的探讨一氧化氮合酶1(NOS1)、神经细胞PAS域蛋白4(NPAS4)和外中心粒物质1(PCM1)基因单核甘酸多态性(SNP)与精神分裂症的关联性。方法选择来自豫北地区在河南省精神病医院住院的偏执型精神分裂症患者516例(病例组)和同地区健康正常人516例(对照组),采用荧光定量聚合酶链反应对NOS1、NPAS4和PCM1基因的5个功能SNP位点进行基因分型,分析SNP与疾病的关联性。进一步分析阳性和阴性症状量表(PANSS)因子分与NOS1、NPAS4和PCM1基因多态性的关联。结果 NOS1(rs3782219、rs3782221)、NPAS4(rs7947391)及PCM1(rs445422、rs370429)5个SNP位点基因型和等位基因频率在病例组和对照组中的分布差异均无统计学意义(P>0.05)。病例组与对照组NOS1基因的2个SNP位点(rs3782219、rs3782221)组成3种单体型(A-A、G-A、G-G)及PCM1基因2个SNP位点(rs445422、rs370429)组成3种单体型(A-A、G-A、G-G)频率的差异均无统计学意义(P>0.50)。NOS1基因的rs3782219基因型与兴奋/敌对因子,rs3782221基因型与抑郁/焦虑因子、兴奋/敌对因子的差异有统计学意义(P<0.05);NPAS4基因的rs7947391与阳性因子分的差异有统计学意义(P<0.05);PCM1基因的rs445422与PANSS总分、阴性因子分、认知因子分的差异有统计学意义(P<0.05),rs370429与PANSS总分、阴性因子、认知因子分的差异有统计学意义(P<0.05)。结论 NOS1基因的rs3782219和rs3782221位点、NPAS4基因的rs7947391位点以及PCM1基因的rs445422和rs370429位点可能不是精神分裂症的易感位点,但这些基因SNP位点基因型可能参与了精神分裂症表型特征。

Objective To investigate the potential association of nitric oxide synthase 1 （NOSI） ,neuronal PAS domain protein 4 （NPAS4） and pericentriolar material 1 （PCM1） gene polymorphisms with the schizophrenia. Methods Five hundred and sixteen paranoid schizophrenia who from the north area of Henan province and hospitalized in Henan Psychiatric Hospital were selected as case group and 516 health adult who from the same area were selected as control group. The five single nueleo- tide polymorphisms （SNPs） of three genes（NOS1 ,NPAS4 and PCM1 ） were genotyped by real time quantitative polymerase chain reaction. The association between SNPs with disease was analysed and the association between postive and negative syn- drome scale（PANSS） factor scores and NOSI ,NPAS4,PCM1 gene polymorphism was analysed further. Results There were no significant differences in genotype or allele frequencies of five SNPs [ NOS1 （rs3782219, rs3782221 ）, NPAS4 （rs7947391）, PCM1 （ rs445422, rs371M29） ] between case group and control group （ P〉 0.05 ）. Meanwhile, there were no significant differ- ences of the haplotypes [ rs3782219, rs3782221 （ A-A, G-A, G-G） ; rs445422, rs370429 （ A-A, G-A, G-G） ] between the case group and control group （P 〉 0.05 ）. There were association between the rs3782219 genotype and excitement/hostility; rs3782221 genotype and dpressiort/anxiety, excitement/hostility（P 〈 0.05 ）. There were association between rs7947391 geno- type and postive factor（ P 〈 0.05）. There were association between rs445422 genotype and PANSS total score, negative factor score and cognition factor score （P 〈 0.05 ） ; rs370429 genotype and PANSS total score, negative factor score, cognition factor score（P 〈0.05）. Conclusion The rs378221, rs3782221 site of NOS1 gene, rs7947391 site of NPAS4 gene and rs445422, rs370429 site of PCM1 gene may not he association with schizophrenia. However, those SNPs may he association with the phe- notype of schizophrenia.