CRIPT、FAM82B、RABEP1基因多态性与精神分裂症的关联研究及抗精神病药物对糖脂代谢的影响

发布时间：2018-01-12 14:13

本文关键词：CRIPT、FAM82B、RABEP1基因多态性与精神分裂症的关联研究及抗精神病药物对糖脂代谢的影响　出处：《新疆医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：全基因组关联研究发现RABEP1基因rs1058398和rs1065482、FAM82B基因rs13042和CRIPT基因rs3087822位点的多态性可能与精神分裂症有关联,但有关以上基因位点多态性与精神分裂症相关性的研究结果尚不明确,本研究选取中国汉族人群精神分裂症患者与正常对照做为研究对象,探讨以上三个基因上的4个位点多态性与中国汉族精神分裂症患病是否有关。同时分析比较精神分裂症患者服用抗精神病药物治疗前后血糖、血脂水平变化,并进一步初探不同位点基因型与糖脂代谢的相关性。方法：(1)本研究采用病例对照研究,病例组选择2009年至2013年间江苏省淮安市第三人民医院精神病科的经诊断为精神分裂症住院患者2358例,对照选择同地区的社区健康体检人员2139例,采用TaqMan探针技术进行基因分型,比较病例组和对照组基因型和等位基因频率分布的差异,进一步探讨基因-基因的交互作用。(2)比较2013年间江苏省淮安市第三人民医院575例首次入院患者抗精神病药物治疗4周前后GLU、TG、TC、HDL、LDL的变化。(3)选取575例首次入院患者中有基因分型结果的研究对象,比较不同位点基因型之间糖脂代谢变化。应用的统计学方法：t检验、单因素方差分析、卡方检验、Logistic回归、叉生分析等。结果：(1)FAM82B基因的rs13042位点的多态性与精神分裂症患病有关,其A等位基因可能是精神分裂症患病的保护因素(P=1.750x10-7),OR(95%CI)为0.800(0.736-0.870)。CRIPT基因的rs3087822位点的多态性与精神分裂症患病有关,其G等位基因可能是精神分裂症的危险因素(P=3.205×10-5),OR(95%CI)为1.255(1.127-1.397)。(2)抗精神病药物能引起糖脂代谢紊乱,入院治疗后空腹血糖呈降低趋势(t=4.085,P=5.046×10-5),胆固醇、甘油三酯、低密度脂蛋白均较治疗前升高(t=6.123,P=1.704×10-9；t=10.691,P=1.875×10-24t=6.064,P=2.411×10-9)。结论：FAM82B基因的rs13042位点的A等位基因显著降低个体罹患精神分裂症的危险,而CRIPT基因的rs3087822位点的G等位基因会增加个体罹患精神分裂症危险。服用抗精神病药物的精神分裂症新发病例4周后血糖、血脂发生变化,提示在临床治疗的过程当中应充分重视抗精神病药物而引起的代谢异常风险增加。
[Abstract]:Objective: a genome-wide association study found that the RABEP1 gene rs1058398 and rs1065482 polymorphism of FAM82B gene rs13042 and CRIPT gene rs3087822 locus may be associated with schizophrenia, but the above gene polymorphism and schizophrenia research results is not clear, this study selected China Han nationality schizophrenic patients and normal controls as the research object, discusses the above three gene 4 polymorphism and China Han schizophrenia. At the same time comparing whether patients with schizophrenia before and after taking antipsychotic drugs in the treatment of blood glucose, blood lipid level changes, and further study on different genotype correlation with glucose and lipid metabolism. Methods: (1) in this study, case-control study, cases from 2009 to 2013 by the Department of psychiatry Huai'an Third People's Hospital of Jiangsu Province A diagnosis of schizophrenia patients in 2358 cases, the control of community health personnel with the area of 2139 cases were genotyped by TaqMan probe technology, compared with the case group and the control group of genotype and allele frequency differences, to further explore the interaction of gene gene. (2) of 2013 years in Jiangsu Huai'an Third People's Hospital, 575 cases of first hospitalization patients treated with antipsychotic drugs before and after 4 weeks of GLU, TG, TC, HDL, LDL. (3) a total of 575 cases of patients admitted to hospital for the first time in the study of genotyping results, glucose and lipid metabolism between different genotypes. The application of statistical Analysis: t test and the single factor variance analysis, chi square test, Logistic regression, crossover analysis. Results: (1) polymorphism and schizophrenia rs13042 locus of FAM82B gene related to the prevalence of the A allele, probably schizophrenia The protection factor for disease (P=1.750x10-7), OR (95%CI) 0.800 (0.736-0.870) polymorphisms and schizophrenia rs3087822 loci of.CRIPT gene related to the prevalence of risk factors, the G allele may be schizophrenia (P=3.205 * 10-5), OR (95%CI) 1.255 (1.127-1.397) (2). Antipsychotic drugs can cause lipid metabolic disorders, hospital treatment after fasting blood glucose decreased (t=4.085, P=5.046 * 10-5), cholesterol, triglyceride, low density lipoprotein were significantly higher than before treatment (t=6.123, P=1.704 * 10-9; t=10.691 P=, 1.875 * 10-24t=6.064, P=2.411 * 10-9). Conclusion: the rs13042 locus of FAM82B gene the A allele significantly lower risk individuals with schizophrenia, and rs3087822 sites of CRIPT gene G allele may increase individual schizophrenia risk. Taking antipsychotic drugs for schizophrenia cases after 4 weeks of blood glucose The changes in blood lipids suggest that in the course of clinical treatment, attention should be paid to the increased metabolic risk caused by antipsychotic drugs.

【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.3

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