IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort

Yongmei Liu, Yvette Berthier-Schaad, Daniele Daniele Fallin, Nancy E. Fink, Russell P. Tracy, Michael John Klag, Michael W. Smith, Josef Coref

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)863-870
Number of pages8
JournalJournal of the American Society of Nephrology
Volume17
Issue number3
DOIs
StatePublished - Mar 2006

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Haplotypes
Dialysis
Interleukin-6
Cardiovascular Diseases
Inflammation
Albumins
Alleles
Genes
Genetic Predisposition to Disease
Genetic Promoter Regions
Causality
Medical Records
Atherosclerosis
Odds Ratio

ASJC Scopus subject areas

  • Nephrology

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IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort. / Liu, Yongmei; Berthier-Schaad, Yvette; Fallin, Daniele Daniele; Fink, Nancy E.; Tracy, Russell P.; Klag, Michael John; Smith, Michael W.; Coref, Josef.

In: Journal of the American Society of Nephrology, Vol. 17, No. 3, 03.2006, p. 863-870.

Research output: Contribution to journalArticle

Liu, Yongmei ; Berthier-Schaad, Yvette ; Fallin, Daniele Daniele ; Fink, Nancy E. ; Tracy, Russell P. ; Klag, Michael John ; Smith, Michael W. ; Coref, Josef. / IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort. In: Journal of the American Society of Nephrology. 2006 ; Vol. 17, No. 3. pp. 863-870.
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