期刊
JOURNAL OF DIABETES AND ITS COMPLICATIONS
卷 15, 期 4, 页码 185-192出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S1056-8727(00)00135-5
关键词
genetic polymorphism; RAGE; diabetic microangiopathy; diabetic complications; diabetes-associated dermatoses
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.
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