Sulfatase modifying factor 1 (SUMF1) is associated with Chronic Obstructive Pulmonary Disease

Weidner, J; Jarenbäck, L; de Jong, K; Vonk, JM; van den Berge, M; Brandsma, CA; Boezen, HM; Sin, D; Bossé, Y; Nickle, D; Ankerst, J; Bjermer, L; Postma, DS; Faiz, A; Tufvesson, E

Sulfatase modifying factor 1 (SUMF1) is associated with Chronic Obstructive Pulmonary Disease

Weidner, J Jarenbäck, L de Jong, K Vonk, JM van den Berge, M Brandsma, CA Boezen, HM Sin, D Bossé, Y Nickle, D Ankerst, J Bjermer, L Postma, DS Faiz, A

Tufvesson, E

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Publication Type:: Journal Article
Citation:: Respiratory Research, 2017, 18 (1)
Issue Date:: 2017-05-02

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Field	Value	Language
dc.contributor.author	Weidner, J	en_US
dc.contributor.author	Jarenbäck, L	en_US
dc.contributor.author	de Jong, K	en_US
dc.contributor.author	Vonk, JM	en_US
dc.contributor.author	van den Berge, M	en_US
dc.contributor.author	Brandsma, CA	en_US
dc.contributor.author	Boezen, HM	en_US
dc.contributor.author	Sin, D	en_US
dc.contributor.author	Bossé, Y	en_US
dc.contributor.author	Nickle, D	en_US
dc.contributor.author	Ankerst, J	en_US
dc.contributor.author	Bjermer, L	en_US
dc.contributor.author	Postma, DS	en_US
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Tufvesson, E	en_US
dc.date.available	2017-04-21	en_US
dc.date.issued	2017-05-02	en_US
dc.identifier.citation	Respiratory Research, 2017, 18 (1)	en_US
dc.identifier.issn	1465-9921	en_US
dc.identifier.uri	http://hdl.handle.net/10453/128964
dc.description.abstract	© 2017 The Author(s). Background: It has been observed that mice lacking the sulfatase modifying factor (Sumf1) developed an emphysema-like phenotype. However, it is unknown if SUMF1 may play a role in Chronic Obstructive Pulmonary Disease (COPD) in humans. The aim was to investigate if the expression and genetic regulation of SUMF1 differs between smokers with and without COPD. Methods: SUMF1 mRNA was investigated in sputum cells and whole blood from controls and COPD patients (all current or former smokers). Expression quantitative trait loci (eQTL) analysis was used to investigate if single nucleotide polymorphisms (SNPs) in SUMF1 were significantly associated with SUMF1 expression. The association of SUMF1 SNPs with COPD was examined in a population based cohort, Lifelines. SUMF1 mRNA from sputum cells, lung tissue, and lung fibroblasts, as well as lung function parameters, were investigated in relation to genotype. Results: Certain splice variants of SUMF1 showed a relatively high expression in lung tissue compared to many other tissues. SUMF1 Splice variant 2 and 3 showed lower levels in sputum cells from COPD patients as compared to controls. Twelve SNPs were found significant by eQTL analysis and overlapped with the array used for genotyping of Lifelines. We found alterations in mRNA expression in sputum cells and lung fibroblasts associated with SNP rs11915920 (top hit in eQTL), which validated the results of the lung tissue eQTL analysis. Of the twelve SNPs, two SNPs, rs793391 and rs308739, were found to be associated with COPD in Lifelines. The SNP rs793391 was also confirmed to be associated with lung function changes. Conclusions: We show that SUMF1 expression is affected in COPD patients compared to controls, and that SNPs in SUMF1 are associated with an increased risk of COPD. Certain COPD-associated SNPs have effects on either SUMF1 gene expression or on lung function. Collectively, this study shows that SUMF1 is associated with an increased risk of developing COPD.	en_US
dc.relation.ispartof	Respiratory Research	en_US
dc.relation.isbasedon	10.1186/s12931-017-0562-5	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Sputum	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Sulfatases	en_US
dc.subject.mesh	Genetic Markers	en_US
dc.subject.mesh	Prevalence	en_US
dc.subject.mesh	Risk Factors	en_US
dc.subject.mesh	Sensitivity and Specificity	en_US
dc.subject.mesh	Reproducibility of Results	en_US
dc.subject.mesh	Smoking	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Sweden	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Genetic Association Studies	en_US
dc.subject.mesh	Biomarkers	en_US
dc.subject.mesh	Oxidoreductases Acting on Sulfur Group Donors	en_US
dc.title	Sulfatase modifying factor 1 (SUMF1) is associated with Chronic Obstructive Pulmonary Disease	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	18	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	18	en_US

Abstract:

© 2017 The Author(s). Background: It has been observed that mice lacking the sulfatase modifying factor (Sumf1) developed an emphysema-like phenotype. However, it is unknown if SUMF1 may play a role in Chronic Obstructive Pulmonary Disease (COPD) in humans. The aim was to investigate if the expression and genetic regulation of SUMF1 differs between smokers with and without COPD. Methods: SUMF1 mRNA was investigated in sputum cells and whole blood from controls and COPD patients (all current or former smokers). Expression quantitative trait loci (eQTL) analysis was used to investigate if single nucleotide polymorphisms (SNPs) in SUMF1 were significantly associated with SUMF1 expression. The association of SUMF1 SNPs with COPD was examined in a population based cohort, Lifelines. SUMF1 mRNA from sputum cells, lung tissue, and lung fibroblasts, as well as lung function parameters, were investigated in relation to genotype. Results: Certain splice variants of SUMF1 showed a relatively high expression in lung tissue compared to many other tissues. SUMF1 Splice variant 2 and 3 showed lower levels in sputum cells from COPD patients as compared to controls. Twelve SNPs were found significant by eQTL analysis and overlapped with the array used for genotyping of Lifelines. We found alterations in mRNA expression in sputum cells and lung fibroblasts associated with SNP rs11915920 (top hit in eQTL), which validated the results of the lung tissue eQTL analysis. Of the twelve SNPs, two SNPs, rs793391 and rs308739, were found to be associated with COPD in Lifelines. The SNP rs793391 was also confirmed to be associated with lung function changes. Conclusions: We show that SUMF1 expression is affected in COPD patients compared to controls, and that SNPs in SUMF1 are associated with an increased risk of COPD. Certain COPD-associated SNPs have effects on either SUMF1 gene expression or on lung function. Collectively, this study shows that SUMF1 is associated with an increased risk of developing COPD.

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http://hdl.handle.net/10453/128964