A 63bp deletion in the promoter of rage correlates with a decreased risk for nephropathy in patients with type 2 diabetes.
Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.
Rudofsky
G
G
Department of Medicine I, Otto-Meyerhof-Zentrum and Department of Nephrology, University of Heidelberg, Germany.
Isermann
B
B
Schilling
T
T
Schiekofer
S
S
Andrassy
M
M
Schneider
J G
JG
Morcos
M
M
Humpert
P M
PM
Sayed
A A R
AA
Witte
S
S
Renn
W
W
Pfohl
M
M
Hamann
A
A
Nosikov
V
V
Schleicher
E
E
Häring
H-U
HU
Rudofsky
G
G
Ritz
E
E
Nawroth
P P
PP
Bierhaus
A
A
D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000517:prevention & control; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics; D012016:Reference Values; D012306:Risk; D017384:Sequence Deletion
D000067759:Receptor for Advanced Glycation End Products