DDOST, PRKCSH and LGALS3, which encode AGE-receptors 1, 2 and 3, respectively, are not associated with diabetic nephropathy in type 1 diabetes.
OBJECTIVE
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
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.
Hoverfelt
A
A
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, Helsinki, Finland.
Sallinen
R
R
Söderlund
J M
JM
Forsblom
C
C
Pettersson-Fernholm
K
K
Parkkonen
M
M
Groop
P-H
PH
Wessman
M
M
D000328:Adult; D002135:Calcium-Binding Proteins; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D037502:Galectin 3 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005959:Glucosidases / Q000235:genetics*; D006602:Hexosyltransferases / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*
D002135:Calcium-Binding Proteins; D037502:Galectin 3; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D006602:Hexosyltransferases; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase; D005959:Glucosidases; C070368:PRKCSH protein, human