Dataset Information

Susceptibility to chronic mucus hypersecretion, a genome wide association study.

ABSTRACT:

Background

Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.

Methods

GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (?20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).

Results

A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p?=?4.25×10(-6), OR?=?1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10(-9)) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.

Conclusions

Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

SUBMITTER: Dijkstra AE

PROVIDER: S-EPMC3979657 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Susceptibility to chronic mucus hypersecretion, a genome wide association study.

Dijkstra Akkelies E AE Smolonska Joanna J van den Berge Maarten M Wijmenga Ciska C Zanen Pieter P Luinge Marjan A MA Platteel Mathieu M Lammers Jan-Willem JW Dahlback Magnus M Tosh Kerrie K Hiemstra Pieter S PS Sterk Peter J PJ Spira Avi A Vestbo Jorgen J Nordestgaard Borge G BG Benn Marianne M Nielsen Sune F SF Dahl Morten M Verschuren W Monique WM Picavet H Susan J HS Smit Henriette A HA Owsijewitsch Michael M Kauczor Hans U HU de Koning Harry J HJ Nizankowska-Mogilnicka Eva E Mejza Filip F Nastalek Pawel P van Diemen Cleo C CC Cho Michael H MH Silverman Edwin K EK Crapo James D JD Beaty Terri H TH Lomas David A DA Bakke Per P Gulsvik Amund A Bossé Yohan Y Obeidat Ma'en M Loth Daan W DW Lahousse Lies L Rivadeneira Fernando F Uitterlinden Andre G AG Hofman Andre A Stricker Bruno H BH Brusselle Guy G GG van Duijn Cornelia M CM Brouwer Uilke U Koppelman Gerard H GH Vonk Judith M JM Nawijn Martijn C MC Groen Harry J M HJ Timens Wim W Boezen H Marike HM Postma Dirkje S DS

PloS one 20140408 4

<h4>Background</h4>Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian population ...[more]

PMID: 24714607

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Dataset Information

Susceptibility to chronic mucus hypersecretion, a genome wide association study.

Background

Methods

Results

Conclusions

Publications

Susceptibility to chronic mucus hypersecretion, a genome wide association study.

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