2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Erratum (v17,p3264) All Versions of this Article: ASN.2005050465v1 17/3/863    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, Y. Articles by Coresh, J. Search for Related Content PubMed PubMed Citation Articles by Liu, Y. Articles by Coresh, J. Related Collections Related Article

IL-6 Haplotypes, Inflammation, and Risk for Cardiovascular Disease in a Multiethnic Dialysis Cohort

Yongmei Liu^*, Yvette Berthier-Schaad^,, Margaret D. Fallin, Nancy E. Fink, Russell P. Tracy, Michael J. Klag, Michael W. Smith^,|| and Josef Coresh

^* Wake Forest University School of Medicine, Winston-Salem, North Carolina; Johns Hopkins Medical Institutions, Baltimore, Maryland; Laboratory of Genomic Diversity; ^|| Basic Research Program, SAIC-Frederick, National Cancer Institute, Frederick, Maryland; and University of Vermont, Burlington, Vermont

Address correspondence to: Dr. Josef Coresh, Johns Hopkins University, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21205. Phone: 410-955-0495; Fax: 410-955-0476; E-mail: coresh@jhu.edu

Received for publication May 5, 2005. Accepted for publication December 29, 2005.

It is unknown whether IL-6, a central regulator of inflammation, is a cause of or just a marker of atherosclerosis. Studies of genetic susceptibility to inflammation, however, avoid the potential for reverse causality. Variation in IL6 gene was studied as a predictor of cardiovascular disease (CVD) risk in a cohort of 775 incident dialysis patients, in whom IL-6 levels are elevated. On the basis of published resequencing data on the IL6 gene, a phylogenetic tree with three main branches (clades 1 to 3) was constructed. Two "clade tag" polymorphisms, –174G/C and 1888G/T, and two missense variants, Pro32Ser and Asp162Val, were genotyped. Circulating IL-6 and albumin were measured a median of 5 mo after the start of dialysis. CVD events were ascertained from medical records. During a median follow-up of 2.5 yr, 294 CVD events occurred. The two coding variants, Pro32Ser (present only in black patients, 10% Ser allele) and Asp162Val (present only in white patients, 1% Val), were associated with lower levels of IL-6 and higher levels of albumin. The common variant in the promoter region, –174G/C, was strongly associated with higher CVD risk and weakly with IL-6 levels. Clade 3 (–174C carriers in the absence of 162 Val allele) was associated with higher IL-6 levels (P = 0.03) and higher CVD risk (hazard ratio 1.44, P = 0.006) after adjustment for covariates. The IL6 gene has functional variants that affect inflammation and risk for CVD among dialysis patients, supporting a causal role for IL6 in CVD.

Related Article

Statin Treatment and Diabetes Affect Myeloperoxidase Activity in Maintenance Hemodialysis Patients

Peter Stenvinkel, Ernesto Rodríguez-Ayala, Ziad A. Massy, Abdul Rashid Qureshi, Peter Barany, Bengt Fellström, Olof Heimburger, Bengt Lindholm, and Anders Alvestrand
Clin. J. Am. Soc. Nephrol. 2006 1: 281-287. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				V. Panichi, G. M. Rizza, S. Paoletti, R. Bigazzi, M. Aloisi, G. Barsotti, P. Rindi, G. Donati, A. Antonelli, E. Panicucci, et al. Chronic inflammation and mortality in haemodialysis: effect of different renal replacement therapies. Results from the RISCAVID study Nephrol. Dial. Transplant., July 1, 2008; 23(7): 2337 - 2343. [Abstract] [Full Text] [PDF]

				W.-Y. Lin, T.-Y. Chiu, L.-T. Lee, C.-C. Lin, C.-Y. Huang, and K.-C. Huang Betel nut chewing is associated with increased risk of cardiovascular disease and all-cause mortality in Taiwanese men Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1204 - 1211. [Abstract] [Full Text] [PDF]

				P. Stenvinkel, J. J. Carrero, J. Axelsson, B. Lindholm, O. Heimburger, and Z. Massy Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient: How Do New Pieces Fit into the Uremic Puzzle? Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 505 - 521. [Abstract] [Full Text] [PDF]

				S. Badiou, J.-P. Cristol, I. Jaussent, N. Terrier, M. Morena, F. Maurice, H. Leray-Moragues, J.-P. Rivory, L. Chalabi, C. Delcourt, et al. Fine-Tuning of the Prediction of Mortality in Hemodialysis Patients by Use of Cytokine Proteomic Determination Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 423 - 430. [Abstract] [Full Text] [PDF]

				M. Girndt, P. Stenvinkel, C. Ulrich, J. Axelsson, L. Nordfors, P. Barany, J. J. Carrero, G. H. Heine, H. Kaul, and H. Kohler Influence of cytokine gene polymorphisms on erythropoetin dose requirements in chronic haemodialysis patients Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3586 - 3592. [Abstract] [Full Text] [PDF]

				B. Hocher, L. Liefeldt, T. Quaschning, P. Kalk, R. Ziebig, M. Godes, K. Relle, G. Asmus, and J.-P. Stasch Soluble CD154 Is a Unique Predictor of Nonfatal and Fatal Atherothrombotic Events in Patients Who Have End-Stage Renal Disease and Are on Hemodialysis J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1323 - 1330. [Abstract] [Full Text] [PDF]

				Y. Liu, Y. Berthier-Schaad, L. Plantinga, N. E. Fink, R. P. Tracy, W. H. Kao, M. J. Klag, M. W. Smith, and J. Coresh Functional Variants in the Lymphotoxin-{alpha} Gene Predict Cardiovascular Disease in Dialysis Patients J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3158 - 3166. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673