【作者】 吴广飞；

【导师】 郑少雄； 陈莉明；

【作者基本信息】 天津医科大学 ， 内分泌与代谢病， 2005， 硕士

【摘要】 目的:炎症反应参与了糖尿病肾病的发生与发展,正常T细胞表达和分泌的活性调节蛋白(RANTES)属于C-C亚族趋化因子,肾小球系膜细胞及肾小管上皮细胞均可分泌RANTES,参与肾小球的硬化和肾间质的纤维化。有研究发现,RANTES启动子—403G/A基因多态性增加了RANTES基因表达水平,本研究旨在观察天津市汉族人RANTES启动子—403G/A基因多态性的分布情况,并探讨基因分布与2型糖尿病肾病的关联性。 方法:病例组(2型糖尿病组)244例,来自代谢病医院住院患者,根据尿白蛋白排泄率(UAER)分为三组,分别为正常白蛋白尿组(DNO组,共86例,男性34例,女性52例,年龄61.53±8.95)、微量白蛋白尿组(DN1组,共84例,男性44例,女性40例,年龄61.85±10.71)和临床白蛋白尿组(DN2组,共74例,男性40例,女性34例,年龄63.35±10.07)。对照组90例(男性38例,女性52例,年龄58.36±8.26),取自代谢病医院健康查体人群。收集临床资料,空腹取静脉血,以常规蛋白酶K快速裂解法提取外周血基因组DNA,应用聚合酶链反应—限制片断长度多态性(PCR-RFLP)法测定RANTES启动子—403G/A基因多态性。最后,对临床资料进行统计分析。 结果:(1) 各组基因分布均符合Hardy-Weinberg遗传平衡定律。(2) 在2型糖尿病组和对照组中均检测到RANTES启动子—403G/A基因多态性标记,存在G/G、G/A、A/A三种基因型和G、A两种等位基因。2型糖尿病组G/G、G/A、A/A三种基因型频率及A等位基因频率分别为50.4%、35.7%、13.9%及31.8%,对照组为41.1%、45.6%、13.3%及36.1%,两组间基因型频率及等位基因频率均无显著性差别(P>0.05)。(3) 正常白蛋白尿组、微量白蛋白尿组及临床白蛋白尿组G/G、G/A、A/A三种基因型频率及A等位基因频率分布分别为,DNO组59.3%、26.7%、14.0%及27.3%,DN1组53.6%、更多还原

【Abstract】 Objectives: Inflammation reactions are associated with the occurrence and development of diabetic nephropathy. Regulated upon activation normal T cell expressed and secreted(RANTES), belonged to C-C subtribe chemokine , can be secreted by both mesangial cell of renal glomerulus and epithelial cells of renal tubule. RANTES is associated with the sclerosis of renal glomerulus and the f ibrosis of renal tubule interstitial. As showed recently,the single nucleotide polymorphism (SNP) in RANTES promoter -403G/A has an increase of RANTES gene expression. It is the aim of this study to investigate the distribution of the single nucleotide polymorphism in RANTES promoter —403G/A in the Han population in Tianjin, and to assess if it is possible that the distribution is associated with diabetic nephropathy in type 2 diabetes mellitus.Method: A total of 244 Han people was involved in the patients group(type 2 diabetes mellitus group) who are selected from the inpatients in Metabolism Disease Hospital, Tianjin Medical University. According to urine albumin excretion rate(UAER), it was classified into three groups, the normoalbuminuria group(DNO group, 86 people,34 male and 52 female, average age was 61.53 ± 8. 95), the microalbuminuria group(DNl group, 84 people, 44 male and 40 female, average age was 61. 85 ±10. 71), and the macroalbuminuria group(DN2 group, 74 people, 40 maleand 34 female, average age was 63. 35+10. 07). A total of 90 Han subjects was involved in the control group (38 male and 52 female, average age was 58.36 + 8.26). Clinical data was collected, and genomic DNA was extracted from peripheral blood cells using a Protease K Fasting Burst Technique. PCR-RFLP analysis was performed to screen the single nucleotide polymorphism in RANTES promoter — 403G/A. Finally, statistics anylysis was performed.Result: (1) The prevalence of the RANTES promoter - 403G/A genotypes and alleles in each group were consistent with Hardy-Weinberg equilibrium law. (2)A polymorphism of RANTES promoter —403G/A were screened both in the diabetes group and the control group. G/G> G/A and A/A genotypes and G^ A alleles were found. The frequency of the genotype and allele in the diabetes group was 50.4% for G/G, 35.7% for G/A, 13.9% for A/A genotype, and 31.8% for A allele. It was 41. 1%, 45. 6%, 13. 3% and 36.1% respectively in the control group. There was no significant difference between the two groups for the respective frequency of the genotypes and alleles(P>0. 05). (3) The frequency of the genotype and allele in the DNO was 59.3% for G/G, 26.7% for G/A, 14.0% for A/A genotype, and 27.3% for A allele. It was 53. 6%, 35. 7%, 10. 7% and 28.6% respectively in the DNl;And was 36. 5%, 45. 9%, 17. 6% and 40.5% respectively in the DN2. There was significant difference between the three groups for the respective frequency of the genotype and allele(P<0. 05). Followed by x2 division method, there was no significant difference between the DNO and DNl(P>0. 05). Merging the DNO and DN1 compared with the DN2 in result that significant difference were found between DN2 and DN0+DN1. A (+) genotype and A allele frequency in DN2 were higher than更多还原