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目的探讨热休克蛋白70(heat shock protein 70,HSP70)家族基因多态性与宁夏回汉族人群2型糖尿病(type 2 diabetes mellitus,T2DM)之间的关联。方法采用病例对照研究设计,按照纳入与排除标准,于2010年3月至2011年10月在宁夏医科大学第二附属医院与教学医院(吴忠市人民医院)收集201例T2DM患者和471例按年龄、性别、民族匹配的健康人为研究对象。应用聚合酶链反应-限制性片段长度多态性(polymerase chain reactionrestriction fragment length polymorphism,PCR-RFLP)技术分析基因HSP70-1(+190G/C)、HSP70-2(+1267A/G)和HSP70-hom(+2437T/C)的基因型及等位基因分布的频率。采用2检验及Logistic回归分析研究指标与T2DM间的关系。结果 HSP70-1、HSP70-hom基因各基因型及等位基因频率在病例组及对照组的分布差异均无统计学意义(P>0.05),而病例组HSP70-2基因GG基因型及G等位基因频率明显高于对照组,差异均有统计学意义(2=14.737,12.769,P<0.01);HSP70-1、HSP70-2、HSP70-hom基因各基因型及等位基因频率在回汉族人群中分布的差异均无统计学意义(P>0.05);病例组与对照组中不同性别人群HSP70-1基因+190位点和HSP70-hom基因+2437位点基因型及等位基因频率分布的差异均无统计学意义,病例组男性HSP70-2基因型频率分布与女性比较差异无统计学意义(P>0.05),而等位基因频率的差异有统计学意义(2=4.165,P<0.05);病例组男性HSP70-1、HSP70-hom基因各基因型及等位基因频率与女性比较差异均无统计学意义(P>0.05);多因素Logistic回归分析显示,T2DM患病的危险因素主要有腰围(waist circumference,WC)、甘油三酯(triglycerides,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、收缩压(systolic blood pressure,SBP)、糖尿病家族史、G等位基因;而高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)为其保护性因素。结论 HSP70-2基因GG基因型及G等位基因携带可能与T2DM的发病有关;宁夏回汉民族间HSP70家族基因各基因型及等位基因频率的分布无明显差异;糖尿病家族史、LDL-C、TC、HSP70-2 G等位基因是影响回汉族人群T2DM发病的重要危险因素;不同性别间HSP70-2基因G等位基因频率的分布可能存在差异,有待进一步研究证实。
Objective To investigate the association between heat shock protein 70 (HSP70) family gene polymorphism and type 2 diabetes mellitus (T2DM) in Ningxia Han nationality. Methods A case-control study was designed. According to inclusion and exclusion criteria, 201 patients with T2DM and 471 patients with T2DM were collected at the Second Affiliated Hospital and Teaching Hospital of Ningxia Medical University (Wuzhong People’s Hospital) from March 2010 to October 2011, , Gender, ethnic matched healthy people as the research object. The expression of HSP70-1 (+ 190G / C), HSP70-2 (+1267A / G) and HSP70-C were determined by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) hom (+ 2437T / C) genotypes and allele distribution frequency. 2 test and Logistic regression analysis were used to analyze the relationship between the index and T2DM. Results There was no significant difference in the distribution of HSP70-1 and HSP70-hom gene genotypes and alleles in case group and control group (P> 0.05), while the cases of G70 genotype and GG genotype (2 = 14.737, 12.769, P <0.01). The genotypes and allele frequencies of HSP70-1, HSP70-2 and HSP70-hom genes were in the same order of magnitude (P> 0.05). The genotypes and allele frequencies of HSP70-1 +190 and HSP70-hom +2437 in different sexes in case group and control group There was no significant difference in the distribution of HSP70-2 between the two groups (P> 0.05), but there was a significant difference in allele frequencies (2 = 4.165, P <0.05). There was no significant difference in genotype and allele frequencies of HSP70-1 and HSP70-hom between male and female patients (P> 0.05). Multivariate logistic regression analysis showed that the prevalence of T2DM The main risk factors are waist circumference (WC), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), family history of diabetes and G allele, while high-density lipoprotein cholesterol -density lipoprotein cholesterol, HDL-C) as its protective factor. Conclusion The GG genotype and G allele of HSP70-2 gene may be related to the pathogenesis of T2DM. There is no significant difference in the distribution of genotype and allele frequency of HSP70 family members among Ning Hui and Han ethnic groups in Ningxia. The family history of diabetes, LDL-C , TC, HSP70-2 G allele is an important risk factor for the onset of T2DM in Hui Han population. The distribution of G allele frequency of HSP70-2 gene may be different between different sexes, which needs further study to confirm.