Advanced glycation end products (AGEs) are believed to play an important ro
le 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 a
rea and is telomeric to the class IT region at 250 kb from DRA. A recent re
port described the characterization of a major RAGE gene variant as a biall
elic 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, w
e have investigated the distribution of this dimorphism in conjunction with
HLA class II genes in large populations of type 1 diabetic patients and he
althy subjects. Although no association of this RAGE gene polymorphism with
disease susceptibility was found, we report a strong linkage disequilibriu
m 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 ex
tensive HLA class II haplo-types associated with this serine variant and id
entified as DRB1*0401-DQA1*0301-DQB1*0301 in the diabetic group and DRB1*'1
501-DQA1*0102-DQB1*0602 in control individuals. These data were partially c
onfirmed by family transmission analysis.