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

Abstract

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 followup airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.

The association of rs7041 polymorphism with infertility and recurrent pregnancy loss in Iranian women with polycystic ovary syndrome

“…This protein, synthesized in the liver, serves as a carrier for vitamin D and its metabolites. The rs7041 polymorphism is one of the genetic variations associated with the VDBP gene, and various studies have investigated its correlation with several diseases, including diabetes (20,36),obesity (21,37), pulmonary obstruction (22,38), asthma (23,39), Parkinson's disease (25,40), and MS (26). The results of these studies suggest that this polymorphism signi cantly impacts various aspects of diseases.…”

“…A well-known single-nucleotide polymorphism (SNP) in exon 11 of VDBP gene named rs7041 is believed to have a substantial impact on low levels of 25-hydroxyvitamin D in diverse populations (19). Until now the association of rs7041 polymorphism with some metabolic disorders such as diabetes, obesity, pulmonary obstruction, asthma, Parkinson`s disease, and MS was investigated by some studies (20)(21)(22)(23)(24)(25)(26). However, a few studies have been carried out on the association between this polymorphism and PCOS (27,28).…”

Biomarker-based clustering of patients with chronic obstructive pulmonary disease

“…(e.g. Alpha-2-Macroglobulin (A2Macro) (42), factor VII (21), ferritin (32,43,44), fetuin A (23), Interleukin-1 beta (IL-1 beta) (6), Interleukin-8 (IL-8) (1), Monocyte chemotactic protein-4 (MCP-4) (7), Macrophage Migration Inhibitory Factor (MIF) (8), Matrix Metalloproteinase-9 (MMP-9) (17), Thymus and activation-regulated chemokine (TARC) (9) and Vitamin D-Binding Protein (VDBP) (24)).…”

“…Most COPD studies only focused on one or a limited number of markers of systemic inflammation revealing the heterogeneity within and between the different systemic inflammatory biomarkers (1)(2)(3). Multiple other inflammatory biomarkers exist, and for example, acute phase proteins and the complement system (1,4,5), cytokines and chemokines and their receptors (6)(7)(8)(9)(10), inhibitors of cytokine signaling (11), adhesion molecules (12,13), immunoglobulins (14), growth factors (10,15,16), proteins involved in tissue remodeling (17,18), hormones and adipokines (19,20), coagulation (21,22), and plasma carrier proteins (23,24) have all been shown to be associated with COPD. These data suggest that to better understand the complexity of COPD on a systemic level, a variety of serum markers encompassing a wider scope of inflammatory processes are needed.…”