Relation between polymorphisms of receptor for advanced glycation end products (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy.
BACKGROUND
Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy.


METHODS
A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival.


RESULTS
The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017).


CONCLUSIONS
The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.
Poon
P Y-K
PY
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Szeto
C-C
CC
Chow
K-M
KM
Kwan
B C-H
BC
Li
P K-T
PK
D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D016009:Chi-Square Distribution; D002681:China; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics*; D018572:Disease-Free Survival; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic