Associations of IL6 polymorphisms with lung function decline and COPD.
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).


CONCLUSIONS
The results suggest that the IL6_-174G/C SNP is associated with a rapid decline in FEV(1) and susceptibility to COPD in smokers.
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J-Q
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UBC James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul's Hospital, 1081 Burrard Street, Vancouver, BC, Canada
Foreman
M G
MG
Shumansky
K
K
Zhang
X
X
Akhabir
L
L
Sin
D D
DD
Man
S F P
SF
DeMeo
D L
DL
Litonjua
A A
AA
Silverman
E K
EK
Connett
J E
JE
Anthonisen
N R
NR
Wise
R A
RA
Paré
P D
PD
Sandford
A J
AJ
D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology
D015850:Interleukin-6