DDOST, PRKCSH and LGALS3, which encode AGE-receptors 1, 2 and 3, respectively, are not associated with diabetic nephropathy in type 1 diabetes

• Published in: Diabetologia 2010-09, Vol.53 (9), p.1903-1907
• Main Authors: Hoverfelt, A, Sallinen, R, Söderlund, J. M, Forsblom, C, Pettersson-Fernholm, K, Parkkonen, M, Groop, P.-H, Wessman, M
• Format: Article
• Language: English
• Subjects: Adult; Advanced glycation end-product receptor; Age; Associated diseases and complications; Biological and medical sciences; Blood & organ donations; Blood pressure; Cardiovascular disease; cardiovascular diseases; Chromosomes; Creatinine; DDOST; Diabetes; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - genetics; Diabetic nephropathy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Galectin 3 - genetics; Genetic association; Genetic Predisposition to Disease - genetics; Genotype; Glucosidases - genetics; Hexosyltransferases - genetics; Human Physiology; Humans; Internal Medicine; Intracellular Signaling Peptides and Proteins - genetics; Kidneys; LGALS3; Male; Medical sciences; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Metabolic Diseases; Middle Aged; Nephrology. Urinary tract diseases; Pathogenesis; Polymorphism; Polymorphism, Single Nucleotide; PRKCSH; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Short Communication; SNP; Urinary system involvement in other diseases. Miscellaneous
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-010-1771-3

Aims/hypothesis The AGE receptors 1, 2 and 3, which are encoded by DDOST, PRKCSH and LGALS3, respectively, may be involved in the pathogenesis of diabetic complications. We sought to find out whether these genes are associated with diabetic nephropathy, cardiovascular disease and type 1 diabetes or related quantitative traits. Methods Using the Tagger program, we selected 28 single nucleotide polymorphisms (SNPs) based on the HapMap Centre d'Etude du Polymorphisme (Utah residents with northern and western European ancestry) data. The SNPs were genotyped in 2,719 Finnish patients with type 1 diabetes and tested for association with diabetic nephropathy (821 cases, 1,060 controls), cardiovascular disease and related quantitative traits. For association analysis with type 1 diabetes, 703 non-diabetic control participants were genotyped. Results We found evidence of genotype association between diabetic nephropathy and the SNPs rs2170336 in DDOST (p = 0.03), rs311788 in PRKCSH (p = 0.04) and rs311778 in PRKCSH (p = 0.02). However, these associations did not reach the significance limit of 0.0008 adjusted for multiple testing. None of the DDOST, PRKCSH or LGALS3 SNPs were associated with quantitative traits related to diabetic nephropathy, including AER and estimated GFR. No associations were found between the SNPs and cardiovascular disease, blood pressure, serum lipid levels or type 1 diabetes. Conclusions/interpretation The common SNPs tested in DDOST, PRKCSH and LGALS3 do not seem to be associated with diabetic micro- or macrovascular complications or with type 1 diabetes in Finnish patients.