IL6 gene-wide haplotype is associated with susceptibility to acute lung injury

Carlos Flores, Shwu Fan Ma, Karen Maresso, Michael S. Wade, Jesus Villar, Joe GN Garcia

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Experimental and clinical studies support the key role of interleukin 6 (IL-6), a potent proinflammatory cytokine, in the development of acute lung injury (ALI). Plasma IL-6 levels are influenced mainly by genetic determinants, and a -174G/C polymorphism of the gene has been recently associated with susceptibility to ALI. Here we aimed to validate the association of the IL6 gene with ALI in a case-control sample from Spain. DNA was isolated from 67 consecutive patients who fulfilled international criteria for severe sepsis and for ALI and 96 population-based controls drawn from the general population. Genotypes of the -174G/C polymorphism along with other 14 tagging variants of the IL6 gene were evaluated. Twenty polymorphisms unlinked to IL6 gene were additionally compared between cases and controls to rule out population stratification. None of the individual single-nucleotide polymorphisms was significantly associated with susceptibility to ALI. However, we found that a common haplotype from -1363 to +4835 from the transcription start site, and spanning the gene, conferred risk for susceptibility to ALI (odds ratio, 2.73; 95% confidence interval, 1.39-5.37; P = 0.003). Adjustment for relevant covariates did not modify this result. These data support the association of the IL6 gene with ALI susceptibility and illustrate the value of haplotype analysis as a robust approach for evaluating IL6 gene effects in association studies.

Original languageEnglish (US)
Pages (from-to)11-17
Number of pages7
JournalTranslational Research
Volume152
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Acute Lung Injury
Haplotypes
Interleukin-6
Genes
Polymorphism
Population Control
Transcription Initiation Site
Spain
Population
Single Nucleotide Polymorphism
Sepsis
Nucleotides
Odds Ratio
Genotype
Confidence Intervals
Cytokines
Plasmas
DNA

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, medical
  • Public Health, Environmental and Occupational Health

Cite this

IL6 gene-wide haplotype is associated with susceptibility to acute lung injury. / Flores, Carlos; Ma, Shwu Fan; Maresso, Karen; Wade, Michael S.; Villar, Jesus; Garcia, Joe GN.

In: Translational Research, Vol. 152, No. 1, 07.2008, p. 11-17.

Research output: Contribution to journalArticle

Flores, Carlos ; Ma, Shwu Fan ; Maresso, Karen ; Wade, Michael S. ; Villar, Jesus ; Garcia, Joe GN. / IL6 gene-wide haplotype is associated with susceptibility to acute lung injury. In: Translational Research. 2008 ; Vol. 152, No. 1. pp. 11-17.
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