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Sputum Vitamin D Binding Protein (VDBP) GC1S/1S Genotype Predicts Airway Obstruction: A Prospective Study in Smokers with COPD

Authors Gao J, Törölä T, Li CX, Ohlmeier S, Toljamo T, Nieminen P, Hattori N, Pulkkinen V, Iwamoto H, Mazur W

Received 12 October 2019

Accepted for publication 20 April 2020

Published 15 May 2020 Volume 2020:15 Pages 1049—1059

DOI https://doi.org/10.2147/COPD.S234464

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell


Jing Gao,1,* Tanja Törölä,1,* Chuan-Xing Li,2 Steffen Ohlmeier,3 Tuula Toljamo,4 Pentti Nieminen,5 Noboru Hattori,6 Ville Pulkkinen,1 Hiroshi Iwamoto,6 Witold Mazur1

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

*These authors contributed equally to this work

Correspondence: Jing Gao
Heart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Finland
Tel +358417071559
Email jing.gao@helsinki.fi, Helsinki

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.

Keywords: vitamin D binding protein, VDBP, genotype, COPD, prospective study, sputum

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