SOCS3基因多态性与汉族人群肥胖易感性的关系

发布时间：2018-12-31 22:24

【摘要】：目的探讨细胞因子信号转导抑制因子3(suppressor of cytokine signaling 3,SOCS3)基因多态性与超重、肥胖易感性的关系,并研究基因-基因、基因-环境交互作用对超重、肥胖发生的影响。研究对象与方法本研究以自然村为抽样单位,采用整群随机抽样的方法从“农村糖尿病、肥胖及生活方式(Rural Diab)”研究中随机抽取年龄为18-74岁的研究对象1737名进行研究。现场调查内容主要包括面对面的问卷调查、体格检查及血样标本采集。从研究对象全血样本中,运用磁珠吸附法提取基因组DNA,采用Taqman荧光探针对符合标准要求的DNA样本进行SOCS3基因rs9914220、rs9892622、rs4969168位点分型。采用Epidata 3.1双录入建立数据库并进行逻辑纠错及一致性检验。连续型变量分布差异采用方差和协方差分析,分类型变量分布差异采用卡方检验;运用Logistic回归模型评估OR值和调整OR值及其95%置信区间,上述分析均通过SAS 9.1完成。检验基因位点Hardy-Weinberg平衡采用Haploview4.2软件分析;单体型分析采用R软件;基因-基因、基因-环境的交互作用采用多因素降维(MDR)模型进行分析。结果在1737名研究对象中,男性797人占45.88%%,女性940人占54.12%;平均年龄为49.82±13.21岁。1.SOCS3基因多态性位点与体格检查指标水平的关联:校正年龄、婚姻状况、高脂饮食、体力活动、血脂异常、2型糖尿病等因素后,体质指数在位点rs9914220多态性分型各组中分布差异具有统计学意义(P=0.049);其余指标水平在位点rs9914220多态性分型各组中分布差异均未见有统计学意义(P0.05)。体格检查指标水平在位点rs9892622和rs4969168多态性分型各组中分布差异无统计学意义(P0.05)。2.SOCS3基因多态性位点与超重、肥胖易感性的关联:调整年龄、婚姻状况、高脂饮食、体力活动、血脂异常、2型糖尿病后,位点rs9914220突变杂合基因型(CT)人群发生肥胖的危险是野生纯合基因型(CC)人群的0.72倍(95%CI:0.53-0.97);显性模型分析,突变杂合+突变纯合基因型(CT+TT)人群发生肥胖的危险是野生纯合基因型(CC)人群的0.76倍(95%CI:0.57-0.99);未见位点rs9914220多态性与超重易感性相关。位点rs9892622和rs4969168多态性与超重、肥胖易感性的关联未见统计学差异。3.单体型分析:调整年龄、婚姻状况、高脂饮食、体力活动、血脂异常、2型糖尿病等因素后,单体型CAA发生肥胖的危险较单体型CGA增加(OR=1.48,95%CI:1.00-2.20)。4.遗传风险评分分析:处于最高遗传风险评分组人群发生肥胖的风险是最低组人群的1.46倍(95%CI:1.02-2.10)。5.基因-基因、基因-环境交互作用:未发现SOCS3基因三个位点之间及位点与环境因素之间具有交互作用。结论1.SOCS3基因位点rs9914220多态性与肥胖易感性有关。2.SOCS3基因三个基因位点(rs9914220、rs9892622、rs4969168)的单体型与肥胖的发生风险相关。3.SOCS3基因三个基因位点的遗传风险评分与肥胖的发生相关。
[Abstract]:Objective to investigate the relationship between the polymorphism of cytokine signal transduction suppressor 3 (suppressor of cytokine signaling 3 (SOCS3) gene and the susceptibility to overweight and obesity, and to study the effect of gene interaction and gene environment interaction on the occurrence of overweight and obesity. Subjects and methods 1737 subjects aged 18-74 years were randomly selected from rural diabetes, obesity and lifestyle (Rural Diab) by cluster random sampling in natural villages. The field investigation mainly includes face-to-face questionnaire, physical examination and blood sample collection. Genomic DNA, was extracted from the whole blood samples by magnetic bead adsorption method. Taqman fluorescence probe was used to type the SOCS3 gene rs9914220,rs9892622,rs4969168 locus in the DNA samples that meet the standard requirements. Using Epidata 3.1 double input to establish database and carry out logical error correction and consistency check. Variance and covariance analysis were used to analyze the distribution of continuous variables, chi-square test was used to test the distribution differences of different types of variables, and Logistic regression model was used to evaluate the OR value and adjust the OR value and its 95% confidence interval, all of which were completed by SAS 9.1. Haploview4.2 software was used to analyze the Hardy-Weinberg balance of gene locus, R software was used to analyze haplotype, and the interaction between gene and gene environment was analyzed by multivariate reduced-dimension (MDR) model. Results among the 1737 subjects, 797 men accounted for 45.88 and 940 women 54.12; The average age was 49.82 卤13.21 years old. The association between 1.SOCS3 gene polymorphism and physical examination index level: adjusted age, marital status, high-fat diet, physical activity, dyslipidemia, type 2 diabetes, etc. There was significant difference in the distribution of body mass index (BMI) among the rs9914220 polymorphism typing groups (P0. 049). There was no significant difference in the distribution of other indexes in the rs9914220 polymorphism typing groups (P0.05). There was no significant difference in the distribution of physical examination indexes between rs9892622 and rs4969168 polymorphism typing groups (P0.05). The association between 2.SOCS3 polymorphism loci and the susceptibility to overweight and obesity: adjustment of age, marital status, high fat diet, Physical activity, dyslipidemia, type 2 diabetes, locus rs9914220 mutation heterozygous genotype (CT) population is 0.72 times the risk of obesity than the wild homozygous (CC) population (95%CI:0.53-0.97); Dominant model analysis showed that the risk of obesity was 0.76 times higher (95%CI:0.57-0.99) than that of wild homozygous (CC) in the population with heterozygote homozygous genotype (CT TT). No locus rs9914220 polymorphism was associated with overweight susceptibility. There was no statistical difference between the polymorphism of rs9892622 and rs4969168 and the susceptibility to overweight and obesity. Haplotype analysis: after adjusting for age, marital status, high fat diet, physical activity, dyslipidemia and type 2 diabetes, haplotype CAA had a higher risk of obesity than haplotype CGA (OR=1.48,95%CI:1.00-2.20). Genetic risk score analysis: people in the highest genetic risk score group were 1. 46 times more likely to develop obesity than those in the lowest group (95%CI:1.02-2.10). Gene-gene, gene-environment interaction: no interaction between three loci of SOCS3 gene and between loci and environmental factors was found. Conclusion the rs9914220 polymorphism of 1.SOCS3 gene is associated with the susceptibility to obesity. Three 2.SOCS3 gene loci (rs9914220,rs9892622,) The haplotype of rs4969168 was associated with the risk of obesity, and the genetic risk score of three loci of 3.SOCS3 gene was associated with the occurrence of obesity.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.2

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