Kanková K, Záhejský J, Márová I, Muzík J, Kuhrová V, Blazková M, Znojil V, Beránek M, Vácha J
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Komenského nám. 2, 662 43 Brno, Czech Republic.
J Diabetes Complications. 2001 Jul-Aug;15(4):185-92. doi: 10.1016/s1056-8727(00)00135-5.
To examine genetic polymorphism in the complete sequence of the Receptor of Advanced Glycation End products (RAGE) gene and its possible associations with diabetes-associated microvascular dermatoses (DAMD). Further, to analyze the distribution of individual genotype combinations on the particular polymorphic loci in the RAGE gene. A part of the RAGE gene spanning a region from -4 to 3334 bp was analyzed on a set of 45 subjects with non-insulin dependent diabetes mellitus (NIDDM) and parallel DAMD by means of PCR with subsequent heteroduplex and single-strand conformation polymorphism (SSCP) analyses. Allele frequencies and genotype combinations of novel common polymorphisms were determined in an associations study comprising four groups of subjects (n=390). Fourteen novel polymorphisms (R77C, V89V, 718G/T, 1704G/T, 1727A1728ins, H305Q, S307C, 2117A/G, 2184A/G, 2245G/A, 2249A/G, 2741G/A, and 3089ACdel) and one described previously (G82S) were identified. Significant association with microvascular dermatoses (MD) irrespective of NIDDM were found for exon mutation 82S (P= .004, after a correction for the number of comparisons P(corr) < .05) and marginally significant for intron variant 1704T (P= .032, P(corr)> .05). Calculated odds ratios for 82S and 1704T were 4.73 (95% CI, 1.51 to 14.77) and 1.73 (95% CI, 0.93 to 3.22), respectively. Certain individual genotype combinations of G82S, 1704G/T, and 2184A/G were significantly associated with the presence of MD (P= .00647) both in diabetic and non-diabetic study populations. The two novel polymorphisms (1704G/T and 2184A/G) together with the G82S were shown to influence the susceptibility to MD independent of diabetes itself.
研究晚期糖基化终末产物受体（RAGE）基因完整序列中的基因多态性及其与糖尿病相关微血管皮肤病（DAMD）的可能关联。此外，分析RAGE基因特定多态性位点上个体基因型组合的分布情况。通过聚合酶链反应（PCR），随后进行异源双链和单链构象多态性（SSCP）分析，对45例非胰岛素依赖型糖尿病（NIDDM）合并并行DAMD的患者进行了RAGE基因中一段从-4至3334 bp区域的分析。在一项包含四组受试者（n = 390）的关联研究中确定了新型常见多态性的等位基因频率和基因型组合。共鉴定出14种新型多态性（R77C、V89V、718G/T、1704G/T、1727A1728ins、H305Q、S307C、2117A/G、2184A/G、2245G/A、2249A/G、2741G/A和3089ACdel）以及一种先前描述过的多态性（G82S）。发现外显子突变82S与微血管皮肤病（MD）显著相关，无论是否患有NIDDM（P = 0.004，经比较次数校正后P(corr) < 0.05），内含子变体1704T具有边缘显著性（P = 0.032，P(corr)> 0.05）。82S和1704T的计算比值比分别为4.73（95%可信区间，1.51至14.77）和1.73（95%可信区间，0.93至3.22）。在糖尿病和非糖尿病研究人群中，G82S、1704G/T和2184A/G的某些个体基因型组合与MD的存在显著相关（P = 0.00647）。已证明两种新型多态性（1704G/T和2184A/G）与G82S一起，独立于糖尿病本身影响对MD的易感性。
