Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated microvascular dermatoses in NIDDM
| Authors | |
|---|---|
| Year of publication | 2001 |
| Type | Article in Periodical |
| Magazine / Source | Journal of Diabetes and its Complications |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Description | 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 analysed 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 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 irrespective of NIDDM were found for exon mutation 82S (P=0.004, after a correction for the number of comparisons Pcorr<0.05) and marginally significant for intron variant 1704T (P=0.032, Pcorr>0.05). 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 microvascular dermatoses (P=0.00647) 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 microvascular dermatoses independent of diabetes itself. |
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