PT  - JOURNAL ARTICLE
AU  - J-Q He
AU  - M G Foreman
AU  - K Shumansky
AU  - X Zhang
AU  - L Akhabir
AU  - D D Sin
AU  - S F P Man
AU  - D L DeMeo
AU  - A A Litonjua
AU  - E K Silverman
AU  - J E Connett
AU  - N R Anthonisen
AU  - R A Wise
AU  - P D Paré
AU  - A J Sandford
TI  - Associations of <em>IL6</em> polymorphisms with lung function decline and COPD
AID  - 10.1136/thx.2008.111278
DP  - 2009 Aug 01
TA  - Thorax
PG  - 698--704
VI  - 64
IP  - 8
4099  - http://thorax.bmj.com/content/64/8/698.short
4100  - http://thorax.bmj.com/content/64/8/698.full
SO  - Thorax2009 Aug 01; 64
AB  - 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 (FEV1) over 5 years and baseline FEV1 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 FEV1 (0.023⩽p⩽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⩽p⩽0.04 in additive genetic models).Conclusion: The results suggest that the IL6_-174G/C SNP is associated with a rapid decline in FEV1 and susceptibility to COPD in smokers.