RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients.
BACKGROUND
Patients with type 2 diabetes (DM2) and end stage renal disease (ESRD) have a dismal survival prognosis, mainly due to cardiovascular events. There is sparse data on genetic predictors. Chemokines and their receptors are important in regulating leukocyte influx and activation in atherosclerosis, and functional polymorphisms in the respective genes are associated with cardiovascular disease risk.


METHODS
We enrolled 225 prevalent Caucasian DM2 patients receiving maintenance hemodialysis in 30 centres in Southern Germany (time from dialysis initiation <2.0 years) from August 1999 to January 2000 for prospective study until December 2003. The CX3CR1 T280M, and MCP-1 -2518 and RANTES -403 and -28 promoter and intronic In1.1T/C polymorphisms were assessed by real-time PCR. Primary end point was all-cause mortality (ACM).


RESULTS
Patients carrying the RANTES -403A or In1.1C allele had a significantly higher ACM risk (multivariate hazard ratio for -403A, dominant model=1.81 [95% CI: 1.22-2.67], p=0.003), mainly due to cardiac events. Similar data were obtained by haplotype analysis. The other SNPs showed no effect on survival.


CONCLUSIONS
In DM2 patients with ESRD, ACM due to cardiac events is associated with RANTES gene variants that are known to alter the expression of this chemokine important in atherosclerosis. Further study of the role of chemokine and chemokine receptor gene variation in determining vascular end points is needed.
Böger
Carsten A
CA
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, D-93042 Regensburg, Germany. carsten.boeger@klinik.uni-regensburg.de
Fischereder
Michael
M
Deinzer
Martina
M
Aslanidis
Charalampos
C
Schmitz
Gerd
G
Stubanus
Mike
M
Banas
Bernhard
B
Krüger
Bernd
B
Riegger
Günter A J
GA
Krämer
Bernhard K
BK
D000368:Aged; D000483:Alleles; D002423:Cause of Death; D018946:Chemokine CCL5 / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006331:Heart Diseases / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007438:Introns / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics* / Q000628:therapy; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D012307:Risk Factors; D016019:Survival Analysis
D018946:Chemokine CCL5