【作者】 陈启众；

【导师】 张毓洪；

【作者基本信息】 宁夏医学院 ， 流行病与卫生统计学， 2006， 硕士

【摘要】 目的研究宁夏银川地区2型糖尿病(Type 2 diabetes mellitus,T2DM)的主要危险因素,并从分子水平探讨脂蛋白脂酶基因(lipoprotein lipase, LPL)及细胞毒T淋巴细胞抗原基因(Cytotoxic T lymphocyte antigen–4 gene ,CTLA-4)多态性与2型糖尿病发病的关系,为T2DM的病因学研究和干预措施提供依据。方法(1)运用频数匹配的病例对照研究方法,于2005年5～7月随机抽取银川市4个社区201例T2DM患者和205例健康对照,两组以年龄、性别、民族进行频数匹配。调查内容包括人口统计学特征、既往疾病史、糖尿病家族史、行为方式、膳食嗜好以及体格检查、实验室指标等资料,采用非条件logistic回归模型进行分析,对单因素分析中有意义的变量进行多因素logistic回归模型分析。(2)于2005年4～8月采集宁夏医学院附属第一、第二医院内分泌科T2DM患者血液标本,对照血样来自于同期外科住院的无糖尿病患者,采用病例对照研究方法及聚合酶链反应—限制性酶切片段长度多态性(PCR-RFLP)技术对158例病例及167例对照进行LPL S447X、HindⅢ位点及CTLA-4第一外显子49A/G位点多态性等位基因、基因型测定,分析其与T2DM发病的关系。结果(1) T2DM危险因素研究的单因素非条件Logistic回归分析结果显示有统计学意义的危险因素有:糖尿病家族史、既往高血压史、冠心病史、脑血管病史、高血脂症、喜食甜食、喜食油脂、喜食动物内脏、烹调油以动物油为主、休闲活动强度、活动时间、腰臀比大、是否吸烟、吸烟指数、个体工商人员、科教医务工作者、收缩压高、甘油三脂、胆固醇、低密度脂蛋白异常等20个因素(P<0.05)。将有统计学意义的20个因素进行多因素Logistic回归分析,结果显示既往高血压史(OR=3.974,CI%:2.193～7.271)、冠心病史(OR=3.459,CI%1.677～7.469)、高血脂症(OR=3.599,CI%:1.854～6.921)、喜食油脂(OR=2.758, CI%: 1.487～6.921)、喜食甜食(OR=1.869,CI%:1.091～3.052)、喜食动物内脏(OR= 2.129, CI%:0.996～4.761)、糖尿病家族史(OR=2.018, CI%:1.165～5.770)、腰臀比大(OR=1.755,CI%:1.019～3.491)、科教医务工作者(OR=2.960, CI%: 1.094～3.125)、甘油三脂异常(OR=2.863,CI%:1.618～7.695)、吸烟指数(OR =1.630,CI%:1.243～4.874)为T2DM独立的主要危险因素。休闲活动(OR=0.669, CI%:0.454～1.959)、活动时间(OR=0.416,CI%:0.248～0.986)为保护因素。(2) T2DM组LPL S447X位点X等位基因和SX基因型分布频率低于对照组(4.1%vs 8.6%,8.3%vs 17.2%),差异有显著性(P= 0.020和0.026);LPL HindⅢ位点突变等位基因及基因型分布两组分布相似,差异无显著性(P=0.790和0.70);CTLA-4第一外显子49A/G多态性位点等位基因及基因型两组分布相似,差异无显著性(P=0.083和0.136)。T2DM组SX基因型携带者TG、TC、LDL-C低于SS基因型携带者,而HDL-C高于SS基因型携带者;均有显著性差异(P<0.05);T2DM组H+H-/H-H-基因型携带者TG显著低于H+H+基因型携带者(P<0.05);T2DM组SX基因型携带者及H+H-/H-H-基因型携带者冠心病发生率分别高于SS基因型携带者和H+H+基因型携带者,差异有显著性(P<0.05)。结论(1)糖尿病阳性家族史、高血压史、冠心病、高血脂症、喜甜食、喜油脂、腹型肥胖、科教医职业、吸烟是宁夏银川市社区人群T2DM的主要危险因素。休闲活动则是其保护因素。(2)LPL外显子9中S447X多态性与宁夏银川地区人群T2DM发病有一定的关联性,是T2DM的一个保护性因素。而LPL内含子8的HindⅢ、CTLA-4第1外显子49位点A/G多态性与宁夏银川人群T2DM发病无显著性关联。(3)LPL S447X、HindⅢ多态性位点突变能对血脂产生有益的影响,并能降低2型糖尿病人并发冠心病的危险性。更多还原

【Abstract】 Objective To investigate the risk factors of type 2 DM in community population inYinchuan, and to explore the association between the variation of lipoprotein lipase gene , Cytotoxic T lymphocyte antigen-4 gene and type 2 DM inYinchuan population in order to provide the scientific basis for the etiology and intervention of type 2 DM.Methods (1) A community-based frequency matching case-control study was conducted. 202 subjects with type 2 DM(cases) and 205 non-diabetes mellitus (controls) were recruited at random in Ningxia Yinchuan community from May to July in 2005. Frequence of age, sex and ethnic were matched between the two groups. All information was collected by questionnaire in face-to-face interview. Univariate Logistic regression, multivariate Logistic regression were used to analyse the risk factors. (2) 158 blood samples of patients with type 2 DM and 169 blood samples of non-diabetes from the first and second affiliated hospitals of Ningxia Medical College were collected .The variation of LPL gene S447X、HindⅢand CTLA-4 exon 1 were detected by PCR- RFLP and their relations to type 2 DM were analyzed.Results (1) Results from univariate analysis showed that the following factors were statistically associated with the incidence of T2DM: family history of DM, history of hypertension, history of coronary heart disease, history of cerebrovascular disease, hypertriglyceride, usually sweat food intake, usually grease food intake, usually harslet food intake, usually cooking with tallow, exercise ,exercise time, WHR, cigarette smoking, smoking index, individual businessman, scientist/teacher/doctor, SBP, TG, TC, LDL-C. The positive results were found with multivariate logistic regression analysis, which were associated with increased risk of type 2 diabetes mellitus, including history of hypertension (OR=3.974, CI%: 2.193~7.271), history of coronary heart disease (OR=3.459, CI%: 1.677~7.469), hypertriglyceride (OR=3.599, CI%: 1.854~6.921), usually sweat food intake (OR=1.869, CI%: 1.091~3.052), usually grease food intake (OR=2.758,CI%:1.487 ~6.921), usually harslet food intake (OR=2.129, CI%:0.996~4.761), WHR (OR=1.755, CI%: 1.019~3.491), smoking index (OR=1.630, CI%: 243~4.874), scientist/teacher/doctor (OR=2.960, CI%: 1.094~3.125), TG (OR=2.863,CI%: 1.618~7.695); while exercise (OR= 0.669, CI%: 0.454~1.959) and exercise time (OR=0.416, CI%: 0.248~0.986) were the reverse association. (2) the frequency of the X allele and SX genotype in cases was lower than that of controls (4.1% vs 8.6% & 8.3% vs 17.2%,).The diffrences were significant (P=0.065 & P=0.057). the frequency of the allele and genotype for HindⅢand CTLA-4 exon 1 49A/G polymorsphism were similar between cases and controls (P=0.790 & 0.70, P=0.083 & 0.136). In cases group, the level of plasma TG ,TC, LDL-C of carriers of the SX genotype were signifiantly lower than that of the carriers of SS genotype and HDL-C of the carriers of SX were higher than that of the carriers of SS genotype (P<0.05); The level of plasma TG of the carriers of H+H-/H-H- genotype were signifiantly lower than in H+H+carriers (P<0.05); In cases group, The incidence of CHD in carriers of the SX genotype and the H+H-/H-H- genotype were lower than that of the carriers of SS genotype and H+H+ genotype respectively. The diffrences were significant (P<0.05).Conclusions (1) Family history of DM, history of hypertension, history of coronary heart disease, hypertriglyceride, usually sweat food intake, usually grease food intake, usually harslet food intake, usually cooking with tallow, WHR, cigarette smoking and scientist/teacher/doctor occupation were the main risk factors of the population with type 2 DM in Ningxia Yinchuan, exercise is the protective factor. (2) LPL gene S447X polymorsphism is associated with the incidence of type 2 DM in Ningxia Yinchuan. But LPL gene HindⅢand CTLA-4 gene exon 1 polymorsphisms were not significantly associated with the incidence of type 2 DM in Ningxia Yinchuan. (3) The Ser447Ter and HindⅢmutation had beneficial effects on plasma lipids, and decreased the incidence of CHD of the population with type 2 DM.更多还原