University of Oulu

Gao J, Törölä T, Li CX, Ohlmeier S, Toljamo T, Nieminen P, Hattori N, Pulkkinen V, Iwamoto H, Mazur W. Sputum Vitamin D Binding Protein (VDBP) GC1S/1S Genotype Predicts Airway Obstruction: A Prospective Study in Smokers with COPD. Int J Chron Obstruct Pulmon Dis. 2020;15:1049-1059,

Sputum vitamin D binding protein (VDBP) GC1S/1S genotype predicts airway obstruction : a prospective study in smokers with COPD

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Author: Gao, Jing1; Törölä, Tanja1; Li, Chuan-Xing2;
Organizations: 1Heart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Pulmonomics Group, Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
3Proteomics Core Facility, Biocentre Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
4Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland
5Medical Informatics and Statistics Group, University of Oulu, Oulu, Finland
6Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.1 MB)
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Language: English
Published: Dove Medical Press, 2020
Publish Date: 2020-07-07


Introduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions.

Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed. Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up.

Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.

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Series: International journal of chronic obstructive pulmonary disease
ISSN: 1176-9106
ISSN-E: 1178-2005
ISSN-L: 1176-9106
Volume: 15
Pages: 1049 - 1059
DOI: 10.2147/COPD.S234464
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was financially supported by EVO funding from the Helsinki University Central Hospital, the Sigrid Jusélius Foundation, the Finnish Anti-TuberculosisAssociation Foundation, the Jalmari and Rauha Ahokas Foundation, and the Finnish Cultural Foundation, the Research Foundation of the Pulmonary Diseases, the Ida Montin Foundation, and the Väinö and Laina Kivi Foundation. We are thankful to the language centre of University of Helsinki providing the linguistic revision for this work. We wish to thank Vanessa L Fuller PhD, for linguistic revision of this work.
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