Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients

Nephrol Dial Transplant. 2009 Sep;24(9):2847-51. doi: 10.1093/ndt/gfp141. Epub 2009 Apr 6.

Abstract

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.

MeSH terms

  • Aged
  • Base Sequence
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / mortality
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / mortality
  • DNA Primers / genetics
  • Female
  • Genotype
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-6 / genetics*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / etiology
  • Myocardial Infarction / genetics
  • Myocardial Infarction / mortality
  • Polymorphism, Single Nucleotide*
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / mortality

Substances

  • DNA Primers
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6