Sulfatase Modifying Factor 1 (SUMF1) is Associated with Chronic Obstructive Pulmonary Disease

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2017 May 4

PMID 28464818

Citations 8

Authors

Julie Weidner

Linnea Jarenback

Kim de Jong

Judith M Vonk

Maarten van den Berge

Corry-Anke Brandsma

H Marike Boezen

Don Sin

Yohan Bosse

David Nickle

Jaro Ankerst

Leif Bjermer

Dirkje S Postma

Alen Faiz

Ellen Tufvesson

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Genetics behind Sulfation: Impact on Airway Remodeling.

Ntenti C, Papakonstantinou E, Fidani L, Stolz D, Goulas A J Pers Med. 2024; 14(3).

PMID: 38540990 PMC: 10971212. DOI: 10.3390/jpm14030248.

Association between SUMF1 polymorphisms and COVID-19 severity.

Liang S, Gao H, He T, Li L, Zhang X, Zhao L BMC Genom Data. 2023; 24(1):34.

PMID: 37344788 PMC: 10283310. DOI: 10.1186/s12863-023-01133-6.

FGF20 and PGM2 variants are associated with childhood asthma in family-based whole-genome sequencing studies.

Hecker J, Chun S, Samiei A, Liu C, Laurie C, Kachroo P Hum Mol Genet. 2022; 32(4):696-707.

PMID: 36255742 PMC: 9896483. DOI: 10.1093/hmg/ddac258.

Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD.

Jarenback L, Frantz S, Weidner J, Ankerst J, Nihlen U, Bjermer L ERJ Open Res. 2022; 8(2).

PMID: 35586453 PMC: 9108960. DOI: 10.1183/23120541.00668-2021.

miRNA-mediated alteration of sulfatase modifying factor 1 expression using self-assembled branched DNA nanostructures.

Kumari K, Kar A, Nayak A, Mishra S, Subudhi U RSC Adv. 2022; 11(18):10670-10680.

PMID: 35423539 PMC: 8695627. DOI: 10.1039/d0ra10733f.

References

Lee J, McDonald M, Cho M, Wan E, Castaldi P, Hunninghake G . DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res. 2014; 15:97. PMC: 4169636. DOI: 10.1186/s12931-014-0097-y. View

Dijkstra A, Smolonska J, van den Berge M, Wijmenga C, Zanen P, Luinge M . Susceptibility to chronic mucus hypersecretion, a genome wide association study. PLoS One. 2014; 9(4):e91621. PMC: 3979657. DOI: 10.1371/journal.pone.0091621. View

Dierks T, Schmidt B, Borissenko L, Peng J, Preusser A, Mariappan M . Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme. Cell. 2003; 113(4):435-44. DOI: 10.1016/s0092-8674(03)00347-7. View

Jurinke C, Van Den Boom D, Cantor C, Koster H . Automated genotyping using the DNA MassArray technology. Methods Mol Biol. 2002; 187:179-92. DOI: 10.1385/1-59259-273-2:179. View

Buono M, Cosma M . Sulfatase activities towards the regulation of cell metabolism and signaling in mammals. Cell Mol Life Sci. 2010; 67(5):769-80. PMC: 11115828. DOI: 10.1007/s00018-009-0203-3. View

Cosma M, Pepe S, Annunziata I, Newbold R, Grompe M, Parenti G . The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell. 2003; 113(4):445-56. DOI: 10.1016/s0092-8674(03)00348-9. View

Preusser-Kunze A, Mariappan M, Schmidt B, Gande S, Mutenda K, Wenzel D . Molecular characterization of the human Calpha-formylglycine-generating enzyme. J Biol Chem. 2005; 280(15):14900-10. DOI: 10.1074/jbc.M413383200. View

Tufvesson E, Aronsson D, Bjermer L . Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis patients with or without bronchial hyperresponsiveness. Clin Exp Allergy. 2007; 37(7):1067-73. DOI: 10.1111/j.1365-2222.2007.02746.x. View

Diez-Roux G, Ballabio A . Sulfatases and human disease. Annu Rev Genomics Hum Genet. 2005; 6:355-79. DOI: 10.1146/annurev.genom.6.080604.162334. View

10.

Fraldi A, Biffi A, Lombardi A, Visigalli I, Pepe S, Settembre C . SUMF1 enhances sulfatase activities in vivo in five sulfatase deficiencies. Biochem J. 2007; 403(2):305-12. PMC: 1874239. DOI: 10.1042/BJ20061783. View

11.

Crapo R, Morris A, Gardner R . Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981; 123(6):659-64. DOI: 10.1164/arrd.1981.123.6.659. View

12.

MacIntyre N, Crapo R, Viegi G, Johnson D, van der Grinten C, Brusasco V . Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005; 26(4):720-35. DOI: 10.1183/09031936.05.00034905. View

13.

Hao K, Bosse Y, Nickle D, Pare P, Postma D, Laviolette M . Lung eQTLs to help reveal the molecular underpinnings of asthma. PLoS Genet. 2012; 8(11):e1003029. PMC: 3510026. DOI: 10.1371/journal.pgen.1003029. View

14.

Schlotawa L, Ennemann E, Radhakrishnan K, Schmidt B, Chakrapani A, Christen H . SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency. Eur J Hum Genet. 2011; 19(3):253-61. PMC: 3062010. DOI: 10.1038/ejhg.2010.219. View

15.

Silverman E, Sandhaus R . Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med. 2009; 360(26):2749-57. DOI: 10.1056/NEJMcp0900449. View

16.

Berger K, Fagondes S, Giugliani R, Hardy K, Lee K, McArdle C . Respiratory and sleep disorders in mucopolysaccharidosis. J Inherit Metab Dis. 2012; 36(2):201-10. PMC: 3590419. DOI: 10.1007/s10545-012-9555-1. View

17.

Miller M, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A . Standardisation of spirometry. Eur Respir J. 2005; 26(2):319-38. DOI: 10.1183/09031936.05.00034805. View

18.

Scholtens S, Smidt N, Swertz M, Bakker S, Dotinga A, Vonk J . Cohort Profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol. 2014; 44(4):1172-80. DOI: 10.1093/ije/dyu229. View

19.

Wanger J, Clausen J, Coates A, Pedersen O, Brusasco V, Burgos F . Standardisation of the measurement of lung volumes. Eur Respir J. 2005; 26(3):511-22. DOI: 10.1183/09031936.05.00035005. View

20.

Cosma M, Pepe S, Parenti G, Settembre C, Annunziata I, Wade-Martins R . Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency. Hum Mutat. 2004; 23(6):576-81. DOI: 10.1002/humu.20040. View