title: Association of IL-6 and a functional polymorphism in the IL-6 gene with cardiovascular events in patients with CKD.
abstract: OBJECTIVE
  High serum IL-6 is a major risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patients with CKD, but it is still unknown whether the link between IL-6 and CVD in CKD is causal in nature.
  
  
  METHODS
  In a cohort of 755 patients with stages 2-5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up±SD, 31±10 months) and used the functional polymorphism (-174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal.
  
  
  RESULTS
  In adjusted analyses, serum IL-6 above the median value was associated with history of CVD (P<0.001) and predicted the incidence rate of CV events (hazard ratio, 1.66; 95% confidence interval [95% CI], 1.11 to 2.49; P=0.01). Patients homozygous for the risk allele (C) of the -174 G/C polymorphism had higher levels of IL-6 than did those with other genotypes (P=0.04). Homozygous CC patients more frequently had a history of CVD (odds ratio, 2.15; 95% CI, 1.15 to 4.00; P=0.02) as well as a 87% higher rate of incident CV events (hazard ratio, 1.87; 95% CI, 1.02 to 3.44; P=0.04) compared with other genotypes.
  
  
  CONCLUSIONS
  In patients with stages 2-5 CKD, high serum IL-6 is associated with history of CVD and predicts incident CV events. The parallel relationship with history of CVD and incident CV events of the -174 G/C polymorphism in the IL-6 gene suggests that IL-6 may be causally involved in the high CV risk in this population.
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Belinda
authors.initials: B
authors.lastname: Spoto
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattace-Raso
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Daniela
authors.initials: D
authors.lastname: Leonardis
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Testa
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Pisano
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pizzini
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cutrupi
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Parlongo
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Graziella
authors.initials: G
authors.lastname: D'Arrigo
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.affiliation: National Research Council of Italy-Institute of Clinical Physiology & Institute of Biomedicine and Molecular Immunology & Nephrology, Dialysis and Transplantation Unit of Reggio, Calabria, Italy; and carmine.zoccali@tin.it.
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6
keywords: cardiovascular; chronic kidney disease; epidemiology and outcomes; polymorphisms; risk factors