中国维族人群CACNA1I基因多态性在精神分裂症中的关联研究

发布时间：2018-04-13 20:12

  本文选题：精神分裂症 + CACNA1I基因　； 参考：《安徽医科大学》2017年硕士论文

【摘要】：背景精神分裂症是一类常见的精神疾病,全球人口患病率高达1%,给患者及其家属带来的沉重的负担与巨大的痛苦。相关研究表明,精神分裂症的家族传递倾向较高,而风险基因的存在对该疾病发生至关紧要。精神疾病基因组协会精神分裂症工作组(Psychiatric Genomics Consortium-Schizophrenia Workgroup,PGC-SCZ)召集了全球的科研力量开展了这个有史以来精神分裂症中规模最大的全基因组关联研究(Genome Wide Association Study,GWAS),这个划时代的结果给我们定位了人类精神分裂症108个易感基因,而钙离子通道CACNA1I基因也位列其中。近年来Sequenom Mass ARRAY基因分型技术已成为识别复杂性遗传疾病相关联的单核苷酸多态性易感位点的有效方法,遗传因素作用的精神疾病应用此方法也获得了众多珍贵的科研成果。目的PGC-SCZ研究报道的有108个基因位点与精神分裂症易感,根据这一研究结果,探究其中的CACNA1I基因在中国维族人群中是否与精神分裂症易感。方法本研究对象选取了来自新疆地区的中国维族人群:正常对照样本共1218份,精神分裂症样本共计985份。Haploview软件筛选出CACNA1I基因内的9个单核苷酸多态性易感位点,运用Sequenom Mass ARRAY基因分型测序平台,并对这个9个位点进行了分型实验。各位点的统计分析由强大的SHEsis软件平台进行处理,包括哈迪温伯格平衡(Hardy-Weinberg equilibrium)检验、等位基因与基因型频率、单倍型分析等方面。结果病例对照数据表明,共6个位点的等位基因频率结果有统计学意义:rs132575(校正后Pallele=0.039,OR=1.159),rs713860(校正后Pallele=0.039,OR=0.792),rs738168(校正后Pallele=0.039,OR=0.785),rs136805(校正后Pallele=0.014,OR=1.212),rs5757760(校正后Pallele=0.042,OR=0.873)and rs5750871(校正后Pallele=0.039,OR=0.859);同时,rs132575和rs136805两位点的基因型频率在病例对照组中的分布差异与精神分裂症显著相关:rs132575(校正后Pgenotype=0.037),rs136805(校正后Pgenotype=0.037)。男女分别统计分析后显示:男性样本中,有7个位点(rs9607658、rs132575、rs713860、rs738168、rs136805、rs5757760、rs5750871)的等位基因频率表现出与精神分裂症显著相关,有4个位点(rs132575、rs136805、rs5757760、rs5750871)的基因型频率统计分析后与疾病易感;而所纳入的女性样本中,没有显示与精神分裂症易感的位点。单倍型分析结果得出,D′值大于0.95的多态性位点共组成4组单倍型块(rs132575-rs713860、rs713860-rs738168、rs713860-rs11705208、rs11705208-rs5750871)。对于rs132575-rs713860单倍型块,单倍型A-T和G-C具有明显的统计学意义;rs713860-rs738168单倍型块中,单倍型C-C和T-A显示出统计学意义;rs713860-rs11705208单倍型块中,单倍型T-C有统计学意义;在rs11705208-rs5750871单倍型块中,单倍型C-G和C-A表现出显著差异。结论我们的研究结果表明CACNA1I基因在中国维族人群中是精神分裂症的一个风险因素。此项研究完善了对精神分裂症致病机理的探究,也为后续精神分裂症发病通路的研究及抗精神类药物基因组学的发展提供了强有力的支持。
[Abstract]:Background schizophrenia is a common mental disease, the global population prevalence rate of 1%, bring a heavy burden to patients and their families with great pain. Related studies have shown that schizophrenia family transfer tendency is high, and there is a risk of the disease gene crucial. Genome wide association of mental illness the schizophrenia group (Psychiatric Genomics Consortium-Schizophrenia Workgroup, PGC-SCZ) convened a global scientific research strength to carry out the genome-wide association studies in schizophrenia in the largest ever (Genome Wide Association Study, GWAS), this landmark positioning results give us human schizophrenia 108 susceptibility genes. Calcium channel CACNA1I gene is also among them. In recent years Sequenom Mass ARRAY genotyping technology has become related to the complexity of recognition of genetic diseases The effective method for susceptibility loci of single nucleotide polymorphisms associated with the genetic factors of mental disorders using this method can obtain a large number of precious achievements in scientific research. PGC-SCZ reported 108 gene locus and schizophrenia susceptibility, according to the results of this study, to explore whether the CACNA1I gene with schizophrenia easily in Chinese Uygur population. Methods the study objects were selected from the Xinjiang area China Uygur population: a total of 1218 normal control samples, schizophrenia samples for a total of 985.Haploview software selected 9 single nucleotide polymorphism in the CACNA1I gene locus, by typing Sequenom Mass ARRAY gene sequencing platform, and the the 9 loci were divided into experiment. Statistical analysis of the members were processed by SHEsis software platform, including the Hardy Weinberg equilibrium (Hardy-Weinberg equili Brium test), genotype and allele frequencies and haplotype analysis. The results of case-control data show that a total of 6 allele frequency results were statistically significant: rs132575 (Pallele=0.039, OR=1.159), rs713860 (Pallele=0.039, OR=0.792), rs738168 (Pallele=0.039, OR=0.785). Rs136805 (Pallele=0.014, OR=1.212), rs5757760 (Pallele=0.042, OR=0.873) and rs5750871 (Pallele=0.039, OR=0.859); at the same time, some significant difference in the distribution between case and control groups in the genotype frequencies of rs132575 and rs136805 two loci with schizophrenia: rs132575 (adjusted Pgenotype=0.037), rs136805 (after correction Pgenotype=0.037). Statistical analysis showed that men and women were male samples, there were 7 loci (rs9607658, rs132575, rs713860, rs738168, rs136805, rs5757760, rs5750871) allele Because of the frequency significantly associated with schizophrenia, 4 loci (rs132575, rs136805, rs5757760, rs5750871) statistics of genotype frequency analysis of susceptibility and disease; and the women included in the sample, and did not show the schizophrenia susceptibility loci. The haplotype analysis results showed that the value of D 'more than 0.95 polymorphic sites were composed of 4 haplotypes (rs132575-rs713860, rs713860-rs738168 group, rs713860-rs11705208, rs11705208-rs5750871). The rs132575-rs713860 haplotype block, with statistically significant haplotype A-T and haplotype block G-C; rs713860-rs738168, C-C and T-A haplotypes showed statistical significance; rs713860-rs11705208 haplotype block, significant haplotype T-C in rs11705208-rs5750871; haplotype block, haplotype C-G and C-A showed significant difference. Conclusion our results suggest that CACNA1I gene in Chinese Uygur population is a risk factor for schizophrenia. This study has improved the exploration of the pathogenesis of schizophrenia, and has also provided strong support for the follow-up study of schizophrenia pathway and the development of antipsychotic genomics.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.3
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本文编号：1746023