Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated microvascular dermatoses in NIDDM

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 analy ze the distribution of individual genotype combinations on the particular p olymorphic 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 poly morphisms were determined in an associations study comprising four groups o f subjects (n = 390). Fourteen novel polymorphisms (R77C, V89V. 718G/T, 170 4G/T, 1727A1728ins, H305Q, S307C, 2117A/G, 2184A/G, 2245G/A, 2249A/G, 2741G /A, and 3089ACdel) and one described previously (G82S) were identified. Sig nificant association with microvascular dermatoses (MD) irrespective of NID DM were found for exon mutation 82S (P = .004, after a correction for the n umber of comparisons P-corr < .05) and marginally significant for intron va riant 1704T (P = .032, P-corr < .05). Calculated odds ratios for 82S and 17 04T were 4.73 (95% CI, 1.51 to 14.77) and 1.73 (95% CI, 0.93 to 3.22), resp ectively. Certain individual genotype combinations of G82S, 1704G/T: and 21 84A/G were significantly associated with the presence of MD ( P = .00647) b oth in diabetic and non-diabetic study populations. The Two novel polymorph isms (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.