基于核心家系的MDGA1基因多态性与精神分裂症的关联研究

发布时间：2018-06-02 11:12

本文选题：精神分裂症 + 单核苷酸多态性　；参考：《南昌大学》2013年硕士论文

【摘要】：一项由Lewis等进行的大型精神分裂症患者全基因组连锁扫描的荟萃分析显示6p22.3-21.1为精神分裂症的连锁区域[1]，MDGA1位于6p21.2，病例-对照研究表明MDGA1基因为精神分裂症易感基因之一。为探讨MDGA1基因是否为中国汉族人群精神分裂症的风险基因，本研究以核心家系为研究对象，，分析MDGA1基因多态性与中国汉族精神分裂症患者的关联。研究共选择36个江西汉族精神分裂症核心家系为研究对象，共108例。选取目标基因MDGA1上6个单核苷酸多态性位点（single nucleotide polymorphisms,SNPs）：rs6900617、rs11759115、rs7769372、rs9462341、rs12191311及rs804831。利用多重聚合酶链式反应（Multiplex PCR），多重连接酶检测反应（Multiplexligase detection reaction，Multiplex LDR）技术检测个体基因型。运用拟合优度x2检验检测各位点基因型频数是否符合Hardy-Weinberg平衡，使用家系的关联分析软件（Family BasedAssociatin Test，FBAT）2.0.4版本，进行MDGA1基因多态性与精神分裂症的传递不平衡检验（Transmission disequilibrium test，TDT）和单倍型相对风险检测（haplotype relative risk，HRR）。 MDGA1基因上6个SNP位点基因型分别在健康父母组及患病组中进行Hardy-Weinberg平衡检验，患病组中位点rs6900617和rs7769372χ~2分别为6.506和3.992，均显示出统计学差异（P0.05），即不符合Hardy-Weinberg平衡。除此两位点外，其余四位点及健康父母组各位点均符合Hardy-Weinberg平衡检验；各等位基因及基因型频数分布分析结果得出，rs9462341与女性精神分裂症相关联（χ~2=4.125，df=1，P0.05）；rs12191311、rs11759115、rs804831及rs9462341四位点进行单个位点TDT检验和HRR分析，结果显示在可加模型，隐性模型下，遗传标记位点rs9462341与精神分裂症关联，等位基因T过多传递，为精神分裂症的危险因素， P值分别为0.015777和0.005960，差异有统计学意义；显性模型下，等位基因A与精神分裂症提示关联（P=0.005960），其对应的Z值为-2.750，等位基因A为精神分裂症的保护因素，位点rs9462341在核心家系中显示出传递不平衡性；而rs12191311、rs11759115及rs804831的TDT检验P值均大于0.05，表明此三位点与精神分裂症无关联。rs12191311-rs11759115-rs804831-rs9462341中的C/T/T/A的单倍型与精神分裂症相关，其P值为0.049861，对应的Z值为-1.961，提示C/T/T/A为精神分裂症的保护因素。其余各单倍型与精神分裂症均未显示出关联（P＞0.05）。结论： 1. MDGA1基因rs9462341位点与精神分裂症相关联(P0.05)，等位基因T过多传递，为精神分裂症的危险因素，等位基因A为精神分裂症的保护因素； 2. rs12191311-rs11759115-rs804831-rs9462341组成的C/T/T/A的单倍型与精神分裂症关联(P0.05)； 3. MDGA1基因rs9462341位点与女性精神分裂症相关联。 4. MDGA1基因位点rs11759115、rs12191311和rs804831与精神分裂症无关联； 5. MDGA1基因可能是中国汉族人群精神分裂症患病基因。
[Abstract]:A meta-analysis of the whole genome linkage scan of large schizophrenic patients by Lewis et al showed that 6p22.3-21.1 was a linkage region of schizophrenia [1] and that MDGA1 was located at 6p21.2. A case-control study showed that the MDGA1 gene was one of the susceptible genes for schizophrenia. In order to investigate whether MDGA1 gene is a risk gene for schizophrenia in Chinese Han population, this study analyzed the association of MDGA1 gene polymorphism with schizophrenia in Chinese Han nationality. A total of 36 nuclear families of Jiangxi Han nationality with schizophrenia were selected as subjects. Six single nucleotide polymorphisms SNPs: rs6900617, rs11759115, rs7769372, rs9462341, rs12191311 and rs804831 were selected from the target gene MDGA1. Individual genotypes were detected by multiplex polymerase chain reaction (PCR) and multiplex ligase detection reactionation multiplex (LDR) technique. Using the goodness of fit x2 test to test whether the frequency of genotypes at each point conforms to the Hardy-Weinberg balance, and using the family association analysis software, Family BasedAssociatin Test / FBAT2.0.4, Transmission disequilibrium test of MDGA1 gene polymorphism and schizophrenia was performed to detect the relative risk of transmission disequilibrium test and haplotype relative. Six SNP loci genotypes of MDGA1 gene were tested for Hardy-Weinberg balance in healthy parent group and disease group respectively. The median rs6900617 and rs7769372 蠂 ~ 2 were 6.506 and 3.992, respectively, which showed statistical difference (P 0.05), which was not in accordance with Hardy-Weinberg balance. With the exception of these two loci, the other four loci and the healthy parent groups all met the Hardy-Weinberg balance test. The analysis of frequency distribution of alleles and genotypes showed that rs9462341 was associated with female schizophrenia (蠂 ~ 2 / 2 = 4.125). The results showed that rs1219131111rs11759115rs804831 and rs9462341 four loci were tested by single locus TDT and HRR analysis, the results showed that, under additive model, recessive model, and recessive model, RS9462341 was detected by single locus TDT test and HRR analysis. Genetic marker locus (rs9462341) was associated with schizophrenia. Allele T was transmitted too much and was a risk factor for schizophrenia (P = 0.015777 and P = 0.005960, respectively). Allele A was associated with schizophrenia. The Z value of allele A was -2.750. Allele A was the protective factor of schizophrenia. The rs9462341 locus showed transmission imbalance in nuclear families. The TDT test P values of rs121913111rs11759115 and rs804831 were all greater than 0.05, which indicated that the haplotypes of C/T/T/A in rs12191311-rs11759115-rs804831-rs9462341 were related to schizophrenia, P = 0.049861and Z = -1.961respectively, indicating that C/T/T/A is the protective factor for schizophrenia. The other haplotypes were not associated with schizophrenia (P > 0.05). Conclusion: 1. The rs9462341 locus of MDGA1 gene was associated with schizophrenia (P 0.05). The allele T was transmitted too much, and allele A was the protective factor of schizophrenia. 2. Haplotype of C/T/T/A composed of rs12191311-rs11759115-rs804831-rs9462341 was associated with schizophrenia (P 0.05); 3. The rs9462341 locus of MDGA1 gene is associated with schizophrenia in women. 4. MDGA1 locus rs11759115 rs12191311 and rs804831 were not associated with schizophrenia. 5. MDGA1 gene may be a gene of schizophrenia in Chinese Han population.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3

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