Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients.
BACKGROUND
Inflammation is a well recognized central component of atherosclerotic processes in chronic kidney disease. Interleukin-6 (IL-6) levels are a strong determinant of cardiovascular mortality in dialysis patients. We evaluated the impact of IL-6 gene G-174C polymorphism associated with modified IL-6 production on the development of coronary artery disease (CAD), cardiovascular events and mortality in chronic dialysis patients.


METHODS
We studied n = 463 patients on chronic dialysis with angiographically confirmed (n = 218) or excluded (n = 245) CAD followed up for 65 months after initiation of dialysis. Monitored were arterial hypertension, diabetes mellitus, hyperlipidemia, smoking, CRP and fibrinogen. IL-6 gene G-174C polymorphism was determined by PCR amplification.


RESULTS
The CC genotype was associated with an impaired patient survival (p < 0.05) remaining an independent risk factor for death in multivariate analysis (HR for CC genotype: 3.58, CI: 1.41-9.07, p < 0.01). CC genotype carrying CAD patients suffered significant frequently cardiovascular events (revascularization, myocardial infarction, death) compared to GG/GC genotype carriers (85.2% vs. 66.5, p < 0.05). However, the IL-6 gene G-174C polymorphism was not related to the onset and development of CAD itself (ns) and the inflammation parameters CRP and fibrinogen did not differ between the genotypes under investigation (ns).


CONCLUSIONS
Our results suggest that IL-6 gene G-174C polymorphism is associated with the incidence of cardiovascular events and mortality in chronic dialysis patients.
Aker
Sendogan
S
Department of Nephrology, Heinrich-Heine University, Germany. basevision@yahoo.com
Bantis
Christos
C
Reis
Philip
P
Kuhr
Nicola
N
Schwandt
Christina
C
Grabensee
Bernd
B
Heering
Peter
P
Ivens
Katrin
K
D000368:Aged; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics* / Q000401:mortality; D003324:Coronary Artery Disease / Q000209:etiology* / Q000235:genetics* / Q000401:mortality; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality
D017931:DNA Primers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6