TY - JOUR
T1 - IL6 gene-wide haplotype is associated with susceptibility to acute lung injury
AU - Flores, Carlos
AU - Ma, Shwu Fan
AU - Maresso, Karen
AU - Wade, Michael S.
AU - Villar, Jesus
AU - Garcia, Joe G.N.
N1 - Funding Information:
Supported by NHLBI HL58064 and HL 073994, by the Lowell Coggeshall Endowment, and by the Fundación Canaria Dr. Manuel Morales (to C.F.).
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=45949100694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45949100694&partnerID=8YFLogxK
U2 - 10.1016/j.trsl.2008.05.006
DO - 10.1016/j.trsl.2008.05.006
M3 - Article
C2 - 18593632
AN - SCOPUS:45949100694
VL - 152
SP - 11
EP - 17
JO - Translational Research
JF - Translational Research
SN - 1931-5244
IS - 1
ER -