Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes
JM Forbes, J Soderlund, FYT Yap, M Knip, S Andrikopoulos, J Ilonen, O Simell, R Veijola, KC Sourris, MT Coughlan, C Forsblom, R Slattery, ST Grey, M Wessman, H Yamamoto, A Bierhaus, ME Cooper, P-H Groop
Diabetologia | SPRINGER | Published : 2011
AIMS/HYPOTHESIS: This group of studies examines human genetic susceptibility conferred by the receptor for advanced glycation end-products (RAGE) in type 1 diabetes and investigates how this may interact with a western environment. METHODS: We analysed the AGER gene, using 13 tag SNPs, in 3,624 Finnish individuals from the FinnDiane study, followed by AGER associations with a high risk HLA genotype (DR3)-DQA1*05-DQB1*02/DRB1*0401-DQB1*0302 (n = 546; HLA-DR3/DR4), matched in healthy newborn infants from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study (n = 373) using allelic analysis. We also studied islets and circulating RAGE in NODLt mice. RESULTS: The rs2070600 and rs174..View full abstract
Awarded by Juvenile Diabetes Research Foundation (JDRF)
Awarded by European Commission
Awarded by Academy of Finland
We are indebted to M Parkkonen and R Sallinen, University of Helsinki, Helsinki, Finland, who contributed to the genotyping of the FinnDiane patients. The authors would also like to thank K Gilbert, V Thallas and M Arnstein, Baker IDI Heart and Diabetes Institute, Melbourne, Australia, for their technical expertise. Thanks also to A Blair for assistance with rat and mouse IV/IPGTTs. This work was completed with support from an innovative grant from the Juvenile Diabetes Research Foundation (JDRF; 5-2010-163). J Forbes is a JDRF Career Development Fellow. S Andrikopoulos is a recipient of an RD Wright Fellowship from the National Health and Medical Research Council of Australia (NHMRC) of Australia. M Cooper is a JDRF Scholar and an NHMRC Australia Fellow. The FinnDiane is funded by the Folkhalsan Research Foundation, Wilhelm and Else Stockmann Foundation, Sigrid Juselius Foundation, European Commission (LSHB-CT-2003-503364, LSHB-CT-2006-037681), Academy of Finland (214335 and 124280 to M.W.), Medicinska understodsforeningen Liv och Halsa, Signe and Ane Gyllenberg Foundation, Waldemar von Frenkell Foundation and Governmental Grants for Health Sciences Research. We acknowledge all the physicians and nurses at each participating centre for their invaluable role in patient recruitment, collection of samples and data (see ESM). The DIPP Study is supported by grants from the Juvenile Diabetes Research Foundation (grants 4-1998-274, 4-1999-731, 4-2001-435), Emil Aaltonen Foundation, Academy of Finland, Jalmari and Rauha Ahokas Foundation, Diabetes Research Foundation, Finland, Signe and Ane Gyllenberg Foundation, Yrjo Jahnsson Foundation, Sigrid Juselius Foundation, Novo Nordisk Foundation, Paivikki and Sakari Sohlberg Foundation, and Special Research Funds for the Oulu, Tampere and Turku University Hospitals.