HSP70家族基因与TNF-α基因的交互作用对代谢综合征发病的影响

发布时间：2018-07-09 16:42

本文选题：代谢综合征 + 基因多态性　；参考：《宁夏医科大学》2015年硕士论文

【摘要】：目的探讨HSP70家族基因和TNF-α基因多态性、单体型及其交互作用与宁夏回汉民族代谢综合征发病的关系,以阐明HSP70与TNF-а基因及其交互作用对MS易感性及转归的影响,为寻找代谢综合征人群防治的易感生物标志物、人群防治的策略及基因-基因连锁或交互作用研究奠定理论基础。方法采用成组病例-对照研究,选取2012年1月-2013年12月间在宁夏医科大学附属总医院及吴忠市人民医院进行定期健康检查和在内分泌科住院的宁夏机关及事业单位的20-60岁职工中,根据纳入及排除标准,确定622例无遗传关系的患有代谢综合征的病人作为病例组,其中回族男性有153例(24.6㳠),回族女性156例(25.1㳠),汉族男性161例(25.9㳠),汉族女性152例(24.4㳠),平均年龄(50.38±6.78)岁;从同一时期健康检查的人群中选择600名无血缘关系的健康人为对照组,回、汉民族各300名(50%),平均年龄(50.35±6.83)岁;对研究对象进行一般情况问卷调查、体格相关检查及实验室相关生化指标检测,并采用Taqman探针法检测HSP70-1基因-110位点、+190位点,HSP70-hom基因+2437位点和TNF-α基因-308位点的多态性;采用SNa Pshot法检测HSP70-2基因+2074位点;采用PCR直接测序法检测HSP70-2基因+1267位点。结果HSP70-1基因-110、+190位点,HSP70-hom基因+2437位点,TNF-α基因-308位点,HSP70-2基因+1267位点、+2074位点基因型及其等位基因频率在回、汉民族中的分布,差异均无显著性(均P0.05);TNF-α基因-308位点、HSP70-1基因-110位点、HSP70-hom基因+2437位点、HSP70-2基因+2074位点各基因型及其等位基因频率在MS组与对照组中分布的差异均有显著性(均P0.05),HSP70-1基因+190位点各基因型及等位基因在MS组与对照组中的分布差异均无显著性(均P0.05),HSP70-2基因+1267位点各基因型在MS组与对照组中分布的差异没有显著性(P0.05),等位基因在MS组与对照组中分布的差异有显著性(P0.05);HSP70家族基因中的+2437、-110、+190、+1267四个位点之间、+2074与+2437位点之间的D’值均大于0.8,说明它们之间存在着强连锁不平衡;HSP70-2基因+2074位点与HSP70-hom基因+2437位点构成的单体型,HSP70-2基因-2074位点、HSP70-hom基因+2437位点、TNF-α基因-308位点构成的单体型,HSP70-1基因-110、+190位点,HSP70-2基因+1267位点,HSP70-hom基因+2437位点构成的单体型,TNF-α基因-308位点,HSP70-1基因-110、+190位点,HSP70-2基因+1267位点,HSP70-hom基因+2437位点构成的单体型与MS均存在相关性;HSP70-1基因+190位点,HSP70-hom基因+2437位点,HSP70-2基因+1267位点,TNF-α基因-308位点组成的4因子模型具有最高的MS发病相对风险性。结论HSP70家族基因-110、190、+1267、+2074、+2437位点及TNF-α基因-308位点在回汉民族间基因型及其等位基因分布情况基本一致;HSP70家族基因-110、+1267、+2074、+2437位点及TNF-α基因-308位点多态性与宁夏人群代谢综合征的发病具有显著关联,-110、+2437位点的C等位基因,+1267、+2074位点的G等位基因及-308位点的A等位基因突变增加了MS的发病风险;+2437、+2074位点间,+2437、-110、+190、+1267四个位点两两间均存在连锁不平衡现象;单体型C-G、A-T-C、A-T-G、G-C-G、C-A-G-A、A-T-C-C-G、G-C-A-G-A可能增加MS的发病风险,单体型T-C、G-T-C、T-A-G-A、G-T-A-G-A可能降低MS的发病风险;-308-+1267-+2437-+190这4个位点的交互作用与代谢综合征有关;+190位点单位点可能与MS不存在关联性,但可能通过与308-+1267-+2437位点的交互作用而增加MS的易感性;+190、+1267位点分别与-308、-110、+2074、+2437位点的交互作用可增加MS的发病风险。-110、+2437位点在MS的发病中具有协同的交互作用,+2074和-308位点在MS的发病中具有拮抗的交互作用。
[Abstract]:Objective to investigate the relationship between the polymorphism of HSP70 family gene and TNF- alpha gene, haplotype and its interaction with the metabolic syndrome of Ningxia Hui and Han nationalities, in order to clarify the effect of HSP70 and TNF- gene and their interaction on the susceptibility and prognosis of MS, and to find a susceptible biomarker for the prevention and control of the population of metabolic syndrome and the strategy of population control and prevention. A theoretical basis was laid on the study of gene gene linkage or interaction. A group of case - control studies were used to select the 20-60 year old workers of the 20-60 year old workers in the affiliated general hospital of Ningxia Medical University and the people's Hospital of Wuzhong City, Wuzhong City, in December, in January 2012, and in the Department of Endocrinology and institutions in the Department of Endocrinology. In the criteria of entry and exclusion, 622 patients with no genetic relationship with metabolic syndrome were identified as case groups, of which 153 (24.6), 156 Hui women (25.1), 161 Han men (25.9?), 152 Han (24.4?), and an average age of (50.38 + 6.78) years of age, were selected from the population of the same period of health examination. The healthy people of the relationship were 300 (50%), the average age of 300 (50%), the average age of (50.35 + 6.83) years. The general situation questionnaire survey, the physical correlation examination and laboratory related biochemical indexes were carried out, and the HSP70-1 gene -110 locus, the +190 site, the HSP70-hom gene +2437 site and the TNF- alpha gene -308 were detected by the Taqman probe method. The polymorphism of the loci; the detection of the +2074 locus of the HSP70-2 gene by SNa Pshot; the detection of the +1267 locus of the HSP70-2 gene by PCR direct sequencing. Results of the -110, +190, HSP70-hom gene +2437 sites, the locus of the alpha gene, the allele, and the allele frequencies of the HSP70-1 gene in the Hui, Han nationality There were no significant differences in distribution (all P0.05); TNF- alpha gene -308 site, HSP70-1 gene -110 site, HSP70-hom gene +2437 locus, HSP70-2 gene +2074 loci and allele frequencies in the MS group and the control group were significantly different (P0.05). The genotype and alleles of the HSP70-1 gene locus were in the group and the allele There was no significant difference in distribution in the control group (all P0.05). There was no significant difference in the distribution of the genotype +1267 loci of the HSP70-2 gene between the MS group and the control group (P0.05). The difference in the distribution of alleles in the MS group and the control group was significant (P0.05), and +2437, -110, +190, and +1267 four sites in the HSP70 family gene. The D 'values between the points are more than 0.8, indicating that there is a strong linkage disequilibrium between them; the +2074 loci of the HSP70-2 gene and the +2437 locus of the HSP70-hom gene, the -2074 loci of the HSP70-2 gene, the +2437 site of the HSP70-hom gene, the -308 loci of the TNF- alpha gene, the HSP70-1 gene, the locus, and the locus of the gene. The +2437 loci of the P70-hom gene, the -308 locus of the TNF- a gene, the HSP70-1 gene -110, the +190 site, the +1267 locus of the HSP70-2 gene, and the +2437 loci of the HSP70-hom gene are related to the MS. The submodel has the highest relative risk of MS onset. Conclusion the distribution of genotype and allele of the HSP70 family gene -110190, +1267, +2074, +2437 and TNF- alpha genes in the Hui Han nationality is basically the same. The HSP70 family gene -110, +1267, +2074, polymorphism and metabolism of the Ningxia population are associated with the metabolism of the population. The pathogenesis of syndrome has a significant association. The C allele of -110, +2437 loci, G allele of +1267, +2074 site and A allele of -308 loci increase the risk of MS; +2437, +2074 loci, +2437, four loci are in linkage disequilibrium; -T-C-C-G, G-C-A-G-A may increase the risk of MS, and somatotype T-C, G-T-C, T-A-G-A, G-T-A-G-A may reduce the risk of MS; the interaction of the 4 loci of -308-+1267-+2437-+190 is related to the metabolic syndrome; the +190 locus point may not be associated with MS, but may be increased by interaction with the 308-+1267-+2437 site. With the susceptibility to MS, the interaction of +190 and +1267 sites with -308, -110, +2074, +2437 loci can increase the risk of MS, and the +2437 loci have synergistic interaction in MS. +2074 and the locus have antagonistic interactions in the pathogenesis of MS.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R589

【参考文献】