Associations of IL6 polymorphisms with lung function decline and COPD.

TitleAssociations of IL6 polymorphisms with lung function decline and COPD.
Publication TypeJournal Article
Year of Publication2009
AuthorsHe, J-Q, Foreman, MG, Shumansky, K, Zhang, X, Akhabir, L, Sin, DD, Man, SFP, DeMeo, DL, Litonjua, AA, Silverman, EK, Connett, JE, Anthonisen, NR, Wise, RA, Paré, PD, Sandford, AJ
JournalThorax
Volume64
Issue8
Pagination698-704
Date Published2009 Aug
ISSN1468-3296
KeywordsCase-Control Studies, Female, Forced Expiratory Volume, Haplotypes, Humans, Interleukin-6, Linkage Disequilibrium, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

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.

DOI10.1136/thx.2008.111278
Alternate JournalThorax
PubMed ID19359268
PubMed Central IDPMC2859187
Grant List5R01 HL 064068-04 / HL / NHLBI NIH HHS / United States
HL007427 / HL / NHLBI NIH HHS / United States
HL072918 / HL / NHLBI NIH HHS / United States
HL075478 / HL / NHLBI NIH HHS / United States
HL71393 / HL / NHLBI NIH HHS / United States
K08 HL072918 / HL / NHLBI NIH HHS / United States
K08 HL072918-01 / HL / NHLBI NIH HHS / United States
N01 HR046002 / HR / NHLBI NIH HHS / United States
N01-HR-46002 / HR / NHLBI NIH HHS / United States
R01 HL064068-01 / HL / NHLBI NIH HHS / United States
R01 HL071393 / HL / NHLBI NIH HHS / United States
R01 HL071393-01 / HL / NHLBI NIH HHS / United States
R01 HL075478 / HL / NHLBI NIH HHS / United States
R01 HL075478-01 / HL / NHLBI NIH HHS / United States
T32 HL007427-19 / HL / NHLBI NIH HHS / United States