Polymorphisms of the receptor of advanced glycation endproducts (RAGE) and the development of nephropathy in type 1 diabetic patients.
OBJECTIVE
We investigated the association of the RAGE (Receptor for Advanced Glycation End products) exon3 gene polymorphisms with stages of nephropathy in type 1 diabetes.


METHODS
The RAGE exon 3 genotype was assessed by Denaturing Gradient Gel Electrophoresis (DGGE) procedure in 487 type 1 diabetic patients with proliferative retinopathy subdivided into four groups according to their level of renal involvement and in 351 control subjects (GENEDIAB study).


RESULTS
We reported here three main low frequency dimorphisms, previously submitted to data banks, Gly82Ser, Val89 CTC/CTG, and Arg77Cys. The genotype distribution of these polymorphisms was not statistically different in type 1 diabetic patients compared to healthy controls (p=0.37). Among the three described polymorphisms, only the RAGE Gly82Ser genotype frequency was significantly increased in the group with advanced nephropathy (11%) defined by a chronic renal failure compared to the three others groups: no nephropathy, 5%; incipient (microalbuminuria) 5%; established (macroalbuminuria), 2%) (P=0.04). The 82 Ser allele was identified as an independent risk marker for the stage of advanced nephropathy: adjusted odds ratio 3.17(95% CI 1,32-7,85, p=0.008).


CONCLUSIONS
These data suggest that the 82 Ser allele of the RAGE gene is a risk allele for developing advanced nephropathy. This suggests that some RAGE gene polymorphisms may be associated with progression to diabetic advanced nephropathy in Caucasian type 1 diabetic patients.
Prevost
G
G
Department of Endocrinology and Diabetology, Clinique Marc Linquette, CHRU Lille, France. gaetan.prevost@skynet.be
Fajardy
I
I
Besmond
C
C
Balkau
B
B
Tichet
J
J
Fontaine
P
P
Danze
P M
PM
Marre
M
M
D019943:Amino Acid Substitution; D001120:Arginine; D003430:Cross-Sectional Studies; D003545:Cysteine; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D005998:Glycine; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012694:Serine
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012694:Serine; D001120:Arginine; D003545:Cysteine; D005998:Glycine