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Human RAGE GLY82SER dimorphism and HLA class II DRB1-DQA1-DQB1 haplotypes in type 1 diabetes

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Advanced glycation end products (AGEs) are believed to play an important role in the development of diabetic complications. AGEs increase in diabetes and modulate cellular functions through binding to a specific cell surface receptor (RAGE). The RAGE gene maps to chromosome 6p in the HLA class III area and is telomeric to the class II region at 250 kb from DRA. A recent report described the characterization of a major RAGE gene variant as a biallelic single base polymorphism (G/A 557) in the exon 3 sequence leading to a change of a glycine to a serine at position 82. Using DGGE and PCR-RFLP, we have investigated the distribution of this dimorphism in conjunction with HLA class II genes in large populations of type 1 diabetic patients and healthy subjects. Although no association of this RAGE gene polymorphism with disease susceptibility was found, we report a strong linkage disequilibrium between the variant carrying the serine amino acid at position 82 and two HLA-DR2 and HLA-DR4 specificities. In particular, we describe two major extensive HLA class II haplotypes associated with this serine variant and identified as DRB1*0401-DQA1*0301-DQB1*0301 in the diabetic group and DRB1*1501-DQA1*0102-DQB1*0602 in control individuals. These data were partially confirmed by family transmission analysis.

Document Type: Research Article


Publication date: October 1, 1999


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