BACKGROUND: Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which probably plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). There is a functional single nucleotide polymorphism (SNP), -174G/C, in the promoter region of IL6. It was hypothesised that IL6 SNPs influence susceptibility for impaired lung function and COPD in smokers. METHODS: Seven and five SNPs in IL6 were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in 1 s (FEV(1)) over 5 years and baseline FEV(1) at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of nine IL6 SNPs was genotyped in 389 cases of COPD from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS). RESULTS: In the LHS, three IL6 SNPs were associated with decline in FEV(1) (0.023< or =p< or =0.041 in additive models). Among them, the IL6_-174C allele was associated with a rapid decline in lung function. The association was more significant in a genotype-based analysis (p = 0.006). In the NETT-NAS study, IL6_-174G/C and four other IL6 SNPs, all of which are in linkage disequilibrium with IL6_-174G/C, were associated with susceptibility to COPD (0.01< or =p< or =0.04 in additive genetic models). CONCLUSION: The results suggest that the IL6_-174G/C SNP is associated with a rapid decline in FEV(1) and susceptibility to COPD in smokers.
BACKGROUND:Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which probably plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). There is a functional single nucleotide polymorphism (SNP), -174G/C, in the promoter region of IL6. It was hypothesised that IL6 SNPs influence susceptibility for impaired lung function and COPD in smokers. METHODS: Seven and five SNPs in IL6 were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in 1 s (FEV(1)) over 5 years and baseline FEV(1) at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of nine IL6 SNPs was genotyped in 389 cases of COPD from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS). RESULTS: In the LHS, three IL6 SNPs were associated with decline in FEV(1) (0.023< or =p< or =0.041 in additive models). Among them, the IL6_-174C allele was associated with a rapid decline in lung function. The association was more significant in a genotype-based analysis (p = 0.006). In the NETT-NAS study, IL6_-174G/C and four other IL6 SNPs, all of which are in linkage disequilibrium with IL6_-174G/C, were associated with susceptibility to COPD (0.01< or =p< or =0.04 in additive genetic models). CONCLUSION: The results suggest that the IL6_-174G/C SNP is associated with a rapid decline in FEV(1) and susceptibility to COPD in smokers.
Authors: R B Sothern; B Roitman-Johnson; E L Kanabrocki; J G Yager; M M Roodell; J A Weatherbee; M R Young; B M Nenchausky; L E Scheving Journal: J Allergy Clin Immunol Date: 1995-05 Impact factor: 10.793
Authors: Andrew J P Smith; Francesco D'Aiuto; Jutta Palmen; Jackie A Cooper; Jane Samuel; Simon Thompson; Julie Sanders; Nikos Donos; Luigi Nibali; David Brull; Pat Woo; Steve E Humphries Journal: Clin Chem Date: 2008-03-20 Impact factor: 8.327
Authors: Cornelia Huth; Thomas Illig; Christian Herder; Christian Gieger; Harald Grallert; Caren Vollmert; Wolfgang Rathmann; Yasmin H Hamid; Oluf Pedersen; Torben Hansen; Barbara Thorand; Christa Meisinger; Angela Doring; Norman Klopp; Henning Gohlke; Wolfgang Lieb; Christian Hengstenberg; Valeriya Lyssenko; Leif Groop; Helen Ireland; Jeffrey W Stephens; Ingrid Wernstedt Asterholm; John-Olov Jansson; Heiner Boeing; Matthias Mohlig; Heather M Stringham; Michael Boehnke; Jaakko Tuomilehto; Jose-Manuel Fernandez-Real; Abel Lopez-Bermejo; Luis Gallart; Joan Vendrell; Steve E Humphries; Florian Kronenberg; H-Erich Wichmann; Iris M Heid Journal: Ann Med Date: 2009 Impact factor: 4.709
Authors: Mac B Robinson; Deepak A Deshpande; Jeffery Chou; Wei Cui; Shelly Smith; Carl Langefeld; Annette T Hastie; Eugene R Bleecker; Gregory A Hawkins Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-05-22 Impact factor: 5.464
Authors: Yu Wang; Karey Shumansky; Don D Sin; S F Paul Man; Loubna Akhabir; John E Connett; Nicholas R Anthonisen; Peter D Paré; Andrew J Sandford; Jian-Qing He Journal: Int J Clin Exp Pathol Date: 2015-10-01