In:
European Respiratory Journal, European Respiratory Society (ERS), Vol. 45, No. 1 ( 2015-01), p. 60-75
Kurzfassung:
Smoking is a notorious risk factor for chronic mucus hypersecretion (CMH). CMH frequently occurs in chronic obstructive pulmonary disease (COPD). The question arises whether the same single-nucleotide polymorphisms (SNPs) are related to CMH in smokers with and without COPD. We performed two genome-wide association studies of CMH under an additive genetic model in male heavy smokers (≥20 pack-years) with COPD (n=849, 39.9% CMH) and without COPD (n=1348, 25.4% CMH), followed by replication and meta-analysis in comparable populations, and assessment of the functional relevance of significantly associated SNPs. Genome-wide association analysis of CMH in COPD and non-COPD subjects yielded no genome-wide significance after replication. In COPD, our top SNP (rs10461985, p=5.43×10 −5 ) was located in the GDNF-AS1 gene that is functionally associated with the GDNF gene. Expression of GDNF in bronchial biopsies of COPD patients was significantly associated with CMH (p=0.007). In non-COPD subjects, four SNPs had a p-value 〈 10 −5 in the meta-analysis, including a SNP (rs4863687) in the MAML3 gene, the T-allele showing modest association with CMH (p=7.57×10 −6 , OR 1.48) and with significantly increased MAML3 expression in lung tissue (p=2.59×10 −12 ). Our data suggest the potential for differential genetic backgrounds of CMH in individuals with and without COPD.
Materialart:
Online-Ressource
ISSN:
0903-1936
,
1399-3003
DOI:
10.1183/09031936.00093314
Sprache:
Englisch
Verlag:
European Respiratory Society (ERS)
Publikationsdatum:
2015
ZDB Id:
2834928-3
ZDB Id:
1499101-9
