Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated microvascular dermatoses in NIDDM
Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated microvascular dermatoses in NIDDM
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DOI：
10.1016/s1056-8727(00)00135-5
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发表时间：
2001-07-01
影响因子：
3
通讯作者：
Vácha, J
中科院分区：
文献类型：
--
作者：
Kañková, K;Záhejsky, J;Vácha, J
检查高级糖基化终末产物受体 (RAGE) 基因完整序列的遗传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 基因中特定多态性位点上各个基因型组合的分布。通过 PCR 以及随后的异源双链和单链构象多态性 (SSCP) 分析，对 45 名患有非胰岛素依赖型糖尿病 (NIDDM) 和平行 DAMD 的受试者分析了跨越 4 至 3334 bp 区域的 RACE 基因的一部分。在一项由四组受试者 (n = 390) 组成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。 14 种新的多态性（R77C、V89V、718G/T、1704G/T、1727A1728ins、H305Q、S307C、2117A/G、2184A/G、2245G/A、2249A/G、2741G/A 和 3089ACdel）和之前描述的一种(G82S) 被识别。不论 NIDDM，外显子突变 82S 均与微血管皮肤病 (MD) 显着相关（P = .004，在校正比较次数 P-corr < .05 后），而内含子变体 1704T 则与微血管皮肤病 (MD) 显着相关（P = .032，P-corr < .05）。 82S 和 1704T 的计算优势比分别为 4.73（95% CI，1.51 至 14.77）和 1.73（95% CI，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 的存在显着相关 (P = .00647)。两种新的多态性（1704G/T 和 2184A/GG）与 C82S 一起被证明可以影响 MD 的易感性，而与糖尿病本身无关。 (C) 2001 Elsevier Science Inc. 保留所有权利。
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 RACE 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/GG) together with the C82S were shown to influence the susceptibility to MD independent of diabetes itself. (C) 2001 Elsevier Science Inc. All rights reserved.