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醛糖还原酶基因多态性及其活性与2型糖尿病微血管并发症的相关性研究

Interrelationship among the Polymorphism of (AC)n in the 5’-end of the AR Gene, the Erythrocyte Aldose Reductase Activity and Susceptibility of Microangiopathy in the Patients with Type 2 Diabetes Mellitus

【作者】 丘瑛

【导师】 罗佐杰;

【作者基本信息】 广西医科大学 , 内分泌, 2007, 硕士

【摘要】 目的:探讨醛糖还原酶(AR)基因5’端二核苷酸(AR)n多态性与广西地区汉族2型糖尿病(T2DM)微血管并发症易感性的关系,寻找AR对广西地区汉族2型DM微血管并发症的危险因子及保护因子。方法:检测186例广西汉族2型糖尿病患者,其中无微血管病变组(NDC)65例,微血管病变组(DMAP)121例(糖尿病肾病组(DN)46例,糖尿病视网膜病变组(DRP)36例,糖尿病神经病变组(DPN)39例),正常对照组(CON)51例,采用银染法(PCR扩增-尿素变性聚丙烯酰胺凝胶电泳-硝酸银染色),检测其AR基因5’端二核苷酸(AR)n多态性,同时用改良Sriratava测定AR活性。结果:广西汉族2型糖尿病患者AR基因5’端(AR)n重复序列多态性为9种等位基因,即Z+8~Z—8。Z+2等位基因在DMAP组显著降低,Z-2等位基因在DMAP组显著增高,在DN组尤其显著,Z+2等位基因为7%,Z-2等位基因为24.1%,差异有统计学意义(P<0.05)。红细胞AR活性在广西汉族2型糖尿病患者中显著增高,其中,以糖尿病肾病患者最为明显。结论:AR基因5’端(AR)n重复序列多态性的等位基因与AR的激活密切相关,Z-2等位基因可能是AR的激活因子,Z+2等位基因则为其抑制因子,而AR的激活对糖尿病微血管病变发生发展有重要作用。

【Abstract】 Objective To study the interrelationship among the polymorphism of(AC)n in the 5’-end of the AR gene,the erythrocyte aldose reductase(AR)activity and susceptibility of microangiopathy in the patients with type 2 diabetes mellitus(DM)of Han people in Guangxi province,China.Look for the activator. and the inhititor of AR.Methods 186 cases of type 2 DM were included in this study.All these cases were the Han nationality of Guangxi zhuang autonomous region.The subjects were divided into DM without diabetic microangiopathy(NDC)(65 cases), diabetic microangiopathy group(DMAP)(121 cases),and normal controls(CON)(51 cases).DMAP group was divided into diabetic peripheral neuropathy(DPN)(39 cases),diabetic nephropathy(DN)(46 cases),diabetic retinopathy(DRP)(36 cases).PCR were performed and PCR products were electrophoresed with 8%formamid/urea gel.AR activity(ARA)was measured by rnodified Sriratava method.The differences of ARA were compared among these groups.Results It showed 9 types of alleles(Z-2~Z+2)in the Han nationality of Guangxi zhuang autonomous region.The frquency of allele Z+2 was much lower in DMAP group than in NDC group and CON group(P<0.05).The frquency of allele Z-2 was much higher in DMAP group than in NDC group and CON group(P<0.05).The frquency of allele Z+2 was much lower in DN group than in DPN group and DRP group(P<0.05).The frquency of allele Z-2 was much higher in DN group than in DPN group and DRP group(P<0.05).ARA in DMAP group was higher than in NDC group and CON group(P<0.05).ARA in DN was significantly higher in DN group than in DPN group and DRP group(P<0.05).Conclusion The relation between the polymorphism of(AC)n in the 5’-end of the AR gene is very intimate in the Han nationality of Guangxi zhuang autonomous region.Z-2 allele may be an activator and Z-2 may be an inhititor of ARo The activation of AR plays an important role in the,development of DMAP.

  • 【分类号】R587.2
  • 【下载频次】146
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