Anti-inflammatory interleukin-10 genotype protects dialysis patients from cardiovascular events.
BACKGROUND
Inflammatory processes play an important role for the progression of atherosclerosis. This can be studied particularly well in patients with chronic renal failure who are on hemodialysis, as they show systemic inflammation due to uremia and dialysis while suffering from premature mortality secondary to rapidly progressing atherosclerosis. Interleukin (IL)-10 is a regulatory cytokine that limits inflammatory processes. The quantitative production of IL-10 is subject to genetic variation based on polymorphisms in the promoter of its gene. We tested the hypothesis that the IL-10 genotype, by influencing the capacity to compensate for dialysis-induced systemic inflammation, determines the risk for cardiovascular complications.


METHODS
Three hundred chronic hemodialysis patients were genotyped for the polymorphic bases at positions -1082 and -819 of the IL-10 promoter sequence. They were prospectively followed for a mean of 20.2 +/- 7.3 months. End-points of the study were major events related to cardiac, cerebrovascular or peripheral artery disease.


RESULTS
The -1082A* allele, which is associated with low production of the cytokine IL-10 and elevated markers of systemic inflammation such as C reactive protein, was predictive for a higher cardiovascular morbidity (relative risk for cardiovascular events 2.76, 95% confidence interval 1.31 to 4.17, P = 0.004) compared to the -1082G* genotype.


CONCLUSIONS
The IL-10 genotype influences the risk for cardiovascular events in hemodialysis patients and allows the definition of a high risk group. The data provide further evidence for a causal role of systemic inflammation for progressive atherosclerosis in dialysis patients.
Girndt
Matthias
M
Medical Department IV, University of Homburg/Saar, Kirrberger Strasse 1, D-66421 Homburg/Saar, Germany.
Kaul
Harald
H
Sester
Urban
U
Ulrich
Christof
C
Sester
Martina
M
Georg
Thomas
T
Köhler
Hans
H
D000368:Aged; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D006435:Renal Dialysis; D012307:Risk Factors
D015415:Biomarkers; D016753:Interleukin-10