The -374 T/A polymorphism in the gene encoding RAGE is associated with diabetic nephropathy and retinopathy in type 1 diabetic patients.

Summary, in English

Aims/hypothesis The receptor for AGE (RAGE) is considered to be mainly an intracellular signal-transducer or pro-inflammatory peptide of possible importance for inflammation and autoimmune diseases. Our aim was to study whether the -374 T/A polymorphism in the gene encoding RAGE (AGER) is associated with diabetes type and presence of diabetic complications. Methods The AGER -374 T/A polymorphism was genotyped in 867 type 1 diabetic patients, 2,467 type 2 diabetic patients and 205 non-diabetic control subjects of Scandinavian origin. Results AGER polymorphism was related to different HLA-DQB1 genotypes and the presence of diabetic complications. Type 1 diabetic patients had a higher frequency of the AGER -374 A/A or T/A genotypes than type 2 diabetic patients (51.1 vs 44.9%, p=0.002) and control subjects (51.1 vs 47.6%, p=0.0006). The RAGE -374 T/A polymorphism was associated with HLA-DQB1 genotypes; patients with HLA risk genotypes had a higher frequency of the A/A or T/A genotypes than patients with other HLA-DQB1 genotypes (60.3 vs 40.3%, p < 0.000001). In type 1 diabetic patients, the frequency of the A/A or T/A genotypes was higher in patients with diabetic nephropathy than without (61.1 vs 46.8%, p=0.006) and with sight-threatening retinopathy than without (56.1 vs 47.6%, p=0.03). In type 2 diabetic patients with HbA(1c) values below the median, the T/T genotype was more frequent in patients with diabetic nephropathy than without (54.3 vs 38.2%, p=0.02). Conclusions/interpretation Our results show an association between the AGER -374 T/A polymorphism and type 1 diabetes. This association was HLA-DQB1-dependent. The polymorphism was associated with diabetic nephropathy in both type 1 and type 2 diabetes, in an HbA(1c)-dependent manner in the latter group, and also with sight-threatening retinopathy in type 1 diabetic patients.

• Författare: Eero Lindholm; Ekaterine Bakhtadze; Marketa Sjögren; Corrado Cilio; Elisabet Agardh; Leif Groop; Carl-David Agardh
• Avdelning/ar: Translationell Muskel Forskning; Diabetes - immunovirologi; Institutionen för kliniska vetenskaper, Malmö
• Publiceringsår: 2006
• Språk: Engelska
• Sidor: 2745-2755
• Publikation/Tidskrift/Serie: Diabetologia
• Volym: 49
• Issue: Sep 13
• Länkar: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16969646&dopt=Abstract; http://dx.doi.org/10.1007/s00125-006-0412-3
• Dokumenttyp: Artikel i tidskrift
• Förlag: Springer
• Ämne: Endocrinology and Diabetes
• Nyckelord: RAGE; polymorphism; diabetes; diabetic complications; type 1; type 2 diabetes; HLA-DQB1
• Status: Published
• Forskningsgrupp: Genomics, Diabetes and Endocrinology; Diabetes - Immunovirology
• ISBN/ISSN/Övrigt: ISSN: 1432-0428