PMID- 20007924

OWN - NLM
STAT- MEDLINE
DCOM- 20100322
LR - 20220408
IS - 1535-4970 (Electronic)
IS - 1073-449X (Linking)
VI - 181
IP - 5
DP - 2010 Mar 1
TI - The 15q24/25 susceptibility variant for lung cancer and chronic obstructive
pulmonary disease is associated with emphysema.
PG - 486-93
LID - 10.1164/rccm.200909-1364OC [doi]
AB - RATIONALE: Genome-wide association studies have identified genetic variants
in
the nicotinic acetylcholine receptor (nAChR) on chromosome 15q24/25 as a risk
for
nicotine dependence, lung cancer, and chronic obstructive pulmonary disease
(COPD). Assessment of bronchial obstruction by spirometry, typically used for

diagnosing COPD, fails, however, to detect emphysema. OBJECTIVES: To

determine
the association of the 15q24/25 locus with emphysema. METHODS: The rs1051730
variant on 15q24/25 was genotyped in two independent white cohorts of 661 and
456
heavy smokers. Participants underwent pulmonary function tests and computed
tomography (CT) of the chest, and took questionnaires assessing smoking
behavior
and health status. MEASUREMENTS AND MAIN RESULTS: The rs1051730 A-allele
correlated with reduced FEV(1) and with increased susceptibility for
bronchial
obstruction with a pooled odds ratio (OR) of 1.33 (95% confidence interval
[CI] =
1.11-1.61; P = 0.0026). In both studies a correlation between the rs1051730
A-allele and lung diffusing capacity (Dl(CO)) and diffusing capacity per unit

alveolar volume (Kco) was observed. Consistently, the rs1051730 A-allele

conferred increased risk for emphysema as assessed by CT (P = 0.0097 and P =
0.019), with a pooled OR of 1.39 (CI = 1.15-1.68; P = 0.00051). Visual
emphysema
scores and scores based on densities quantified on CT were more pronounced in

A-allele carriers, indicating that rs1051730 correlates with the severity of

emphysema. CONCLUSIONS: The 15q24/25 locus in nAChR is associated with the
presence and severity of emphysema. This association was independent of
pack-years smoking, suggesting that nAChR is causally involved in alveolar
destruction as a potentially shared pathogenic mechanism in lung cancer and
COPD.
FAU - Lambrechts, Diether
AU - Lambrechts D
AD - Vesalius Research Center, K.U. Leuven, Leuven, Belgium.
diether.lambrechts@vib-kuleuven.be
FAU - Buysschaert, Ian
AU - Buysschaert I
FAU - Zanen, Pieter
AU - Zanen P
FAU - Coolen, Johan
AU - Coolen J
FAU - Lays, Natacha
AU - Lays N
FAU - Cuppens, Harry
AU - Cuppens H
FAU - Groen, Harry J M
AU - Groen HJ
FAU - Dewever, Walter
AU - Dewever W
FAU - van Klaveren, Rob J
AU - van Klaveren RJ
FAU - Verschakelen, Johny
AU - Verschakelen J
FAU - Wijmenga, Cisca
AU - Wijmenga C
FAU - Postma, Dirkje S
AU - Postma DS
FAU - Decramer, Marc
AU - Decramer M
FAU - Janssens, Wim
AU - Janssens W
LA - eng
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
DEP - 20091210
PL - United States
TA - Am J Respir Crit Care Med
JT - American journal of respiratory and critical care medicine
JID - 9421642
RN - 0 (Receptors, Nicotinic)
SB - IM
MH - Alleles
MH - Bronchi/pathology
MH - Female
MH - Genetic Association Studies
MH - Genetic Predisposition to Disease/genetics
MH - Genotype
MH - Humans
MH - Male
MH - Middle Aged
MH - Polymorphism, Single Nucleotide/*genetics
MH - Pulmonary Disease, Chronic Obstructive/etiology/*genetics
MH - Pulmonary Emphysema/etiology/*genetics
MH - Receptors, Nicotinic/*genetics
MH - Respiratory Function Tests
MH - Smoking/*adverse effects/genetics
MH - Tomography, X-Ray Computed
EDAT- 2009/12/17 06:00
MHDA- 2010/03/23 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/03/23 06:00 [medline]
AID - 200909-1364OC [pii]
AID - 10.1164/rccm.200909-1364OC [doi]
PST - ppublish
SO - Am J Respir Crit Care Med. 2010 Mar 1;181(5):486-93. doi:
10.1164/rccm.200909-1364OC. Epub 2009 Dec 10.