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醛糖还原酶基因多态性与糖尿病微血管并发症的相关性研究 |
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刘丽梅 项坤三 郑泰山
【摘要】 目的 探讨醛糖还原酶(AR)基因多态标记(AC)n与中国人2型糖尿病微血管并发症之间的关系。方法 用32P-引物末端标记法，经聚合酶链反应-变性聚丙烯酰胺凝胶电泳，检测362例中国人(217人为2型糖尿病，其中156人合并肾病或视网膜病变，145人为非糖尿病对照)AR基因的二核苷酸(AC)n串联重复序列多态标记，比较各组间的等位基因频率和基因型频率。结果 (1)在非糖尿病对照者和2型糖尿病患者中，见到七种AR基因的等位基因，其中以(AC)24(138bp)等位基因(Z)最常见。(2)同时合并肾病和视网膜病变的2型糖尿病组与无并发症的2型糖尿病组相比，Z+6等位基因频率显著减少(Fisher确切，P=0.038)，含Z+6等位基因的基因型频率也显著减少(P=0.004)。(3)无并发症的2型糖尿病组与对照组比较其Z+6等位基因频率显著增加(P=0.044)。(4)2型糖尿病合并肾病伴肾功能不全者与不伴有肾病的2型糖尿病者相比，Z-2等位基因频率显著增加(P=0.039)，同时含Z-2等位基因的基因型频率也呈增加趋势。结论 AR的Z-2等位基因是促进中国人2型糖尿病并发严重肾病(肾功能不全)的危险因子，而Z+6等位基因则是2型糖尿病患者发生肾病和视网膜并发症的保护因子。
【关键词】 糖尿病，2型 醛糖还原酶 基因 肾病 视网膜病变
A study of association between polymorphism of aldose reductase gene and diabetic microangiopathy
LIU Limei,XIANG Kunsan,ZHENG Taishan
Department of Endocrinology and Metabolism,Diabetes Research Laboratory and Medical Genetics Research Laboratory,Shanghai Sixth People s Hospital,Shanghai,200233
【Abstract】 Objective To investigate the association between dinucleotide repeat polymorphism at 5 end of aldose reductase (AR) gene and diabetic microangiopathy in Chinese. Methods A case-control study for 362 Chinese subjects (including 217 type 2 diabetes mellitus with or without nephropathy or retinopathy and 145 non-diabetes control) was performed. The number of (AC)n dinucleotide of AR gene was determined by PCR-denaturing polyacrylamide gel electrophoresis. Results Tandem (AC) repeats of the AR gene were highly polymorphic and 7 alleles were observed in type 2 diabetes mellitus and control. The most prevalent allele was 24 times in (AC) repeat and was designated as Z allele. In type 2 diabetes mellitus with both nephropathy and retinopathy, a decreased frequency of Z+6 allele was found in comparison with type 2 diabetes mellitus without microangiopathy (Fisher s exact, P=0.038). In addition, an elevated frequency of Z-2 allele was observed in type 2 diabetes mellitus with severe nephropathy (renal insuffici[1] [2] [3] 下一页
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