DIP2A基因多态性与儿童汉语阅读障碍易感性的关联研究

发布时间：2018-04-27 05:03

本文选题：阅读障碍 + 汉语　；参考：《华中科技大学》2016年硕士论文

【摘要】：目的:探讨DIP2A基因多态性与儿童汉语阅读障碍易感性的关系,为阐明阅读障碍的发病机制及开展预防干预措施提供科学依据。方法:1.本研究采用病例-对照研究的方法,选取“阅读环境与阅读障碍研究”项目中409名汉语阅读障碍儿童和410名阅读能力正常儿童。对其问卷信息进行描述统计分析,以探究影响阅读障碍发生的家庭环境因素。2.采集研究对象的口腔上皮细胞以提取基因组DNA。根据DIP2A基因生物学信息筛选其功能性常见变异位点,并通过Sequenom Mass Array系统对其多态性进行检测。通过拟合优度c2检验判断基因型分布是否符合Hardy-Weinberg遗传平衡定律;使用c2检验比较病例组和对照组等位基因和基因型频率分布。采用非条件logistic回归模型分析DIP2A基因单核苷酸多态性(SNP)与阅读障碍易感性的关系。所有统计分析采用SPSS13.0软件包实现。结果:1.因13个儿童DNA样本未能成功基因分型(6个病例,7个对照),故最终纳入研究的对象为403名阅读障碍组儿童和403名对照组儿童。性别和年龄在病例组和对照组之间的差异无统计学意义(c2性别=0.010,P性别=0.919;t年龄=0.852,P年龄=0.394)。2.结构方程模型结果显示儿童家庭经济社会水平影响家庭阅读环境的营造,进而影响汉语阅读障碍的发生(该模型中比较适配指数CFI为0.976,规准适配指数NFI为0.968,渐进残差均方和平方根RMSEA为0.058)。3.根据DIP2A基因易感位点的筛选条件和基因型分型结果,仅rs2255526和rs16979358位点纳入研究分析。rs2255526等位基因频率在病例组和对照组之间分布差异具有统计学意义(c2=5.09,P=0.024),各基因型频率在两组之间分布差异无统计学意义(c2=5.28,P=0.071)。rs16979358位点的等位基因频率和各基因型频率分布在两组之间差异均无统计学意义(P0.05)。调整年龄、性别的影响后,rs2255526位点携带基因型GG个体发生阅读障碍的风险是携带基因型为AA个体的1.833倍(OR=1.833,95%CI=1.043-3.223,P=0.035)。加性模型显示,携带等位基因G是发生阅读障碍的危险因素(OR=1.297,95%CI=1.036-1.623,P=0.023)。显性模型中,基因型为AG+GG的个体与基因型为AA个体相比,其发生阅读障碍的危险性升高,差异接近统计学意义(OR=1.314,95%CI=0.992-1.741,P=0.057)。隐性模型中,携带基因型GG的个体发生阅读障碍的风险是基因型AA+AG个体的1.677倍,差异亦接近于统计学意义(OR=1.677,95%CI=0.967-2.908,P=0.066)。此外,本研究未发现rs16979358位点的多态性与阅读障碍的易感性有关(P0.05)。结论:DIP2A基因rs2255526位点的多态性可能是汉语阅读障碍的遗传易感因素之一。
[Abstract]:Objective: to explore the relationship between polymorphism of DIP2A gene and susceptibility of children with Chinese dyslexia, and to provide scientific basis for elucidating the pathogenesis of dyslexia and carrying out preventive intervention measures. Method 1: 1. In this study, 409 children with Chinese dyslexia and 410 normal children were selected from the study of reading environment and dyslexia by a case-control study. In order to explore the family environmental factors that affect the occurrence of dyslexia, the questionnaire information is described and analyzed. The oral epithelial cells were collected to extract genomic DNA. According to the biological information of DIP2A gene, the functional common mutation sites were screened, and its polymorphism was detected by Sequenom Mass Array system. The allele and genotype frequency distribution in the case group and the control group were compared by c2 test to determine whether the genotype distribution was in accordance with the Hardy-Weinberg genetic balance law. The relationship between single nucleotide polymorphisms (SNPs) of DIP2A gene and susceptibility to dyslexia was analyzed by non conditional logistic regression model. All statistical analysis is implemented by SPSS13.0 software package. The result is 1: 1. Because 13 children's DNA samples could not be genotyped successfully (6 cases, 7 controls), 403 children with dyslexia and 403 control children were included in the study. There was no significant difference in sex and age between the case group and the control group. The results of structural equation model show that the economic and social level of children's family affects the construction of family reading environment. In this model, the relative adaptation index (CFI) is 0. 976, the standard adaptation index (NFI) is 0. 968, and the progressive residual mean square and square root RMSEA are 0. 058 ~ 0. 3. According to the screening conditions of susceptibility sites of DIP2A gene and the results of genotyping, Only the rs2255526 and rs16979358 loci were included in the study. The allele frequency of rs2255526 was significantly different between the case group and the control group. There was no significant difference in the alleles of the alleles at locus 0.071. rs16979358 between the two groups. There was no significant difference in frequency and genotype frequency distribution between the two groups (P 0.05). After adjustment of age and sex, the risk of dyslexia in GG individuals carrying genotype rs2255526 was 1.833 times as high as that in AA individuals. The additive model showed that carrying allele G was a risk factor for dyslexia. In the dominant model, the risk of dyslexia in individuals with genotype AG GG was higher than that in individuals with genotype AA, and the difference was close to the statistical significance. In the recessive model, individuals carrying genotype GG were 1.677 times more likely to develop dyslexia than those with genotype AA AG, and the difference was close to the statistical significance. In addition, no association between polymorphism of rs16979358 locus and susceptibility to dyslexia was found in this study. Conclusion the polymorphism of the rs2255526 locus of the 1: DIP2A gene may be one of the genetic susceptibility factors for Chinese dyslexia.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.94

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