The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity

Abstract

Vitamin D modulates immune responses and its deficiency has been observed in more than 60% of bronchiectasis patients. Vitamin D binding protein (DBP) is coded by the GC gene, is involved in the transport of vitamin D, and includes a number of isoforms based on single nucleotide polymorphisms (SNPs) in the coding region at rs7041 and rs4855. We evaluated the possible clinical impact of DBP polymorphisms and isoforms in an observational, cross-sectional study conducted in 116 bronchiectasis patients, who were genetically characterized for rs4588 and rs7041 SNPs. Results showed that the GC1f isoform (rs7041/rs4588 A/G) correlated with a more severe disease (18.9% vs. 6.3%, p = 0.038), a higher incidence of chronic infections (63.6% vs. 42%, p = 0.041), and a lower BACI score (0.0 (0.0, 2.5) vs. 3.0 (0.0, 3.0), p = 0.035). Moreover, blood concentration of vitamin D was higher in patients carrying GC1s (median (IQR): 20.5 (14.3, 29.7 vs. 15.8 (7.6, 22.4), p = 0.037)). Patients carrying GC1f isoform have a more severe disease, more chronic infections and lower asthmatic comorbidity in comparison to those without the GC1f isoform. Presence of the GC1s isoform (rs7041/rs4588 C/G) seems to be associated to a milder clinical phenotype with increased vitamin D levels and lower comorbidities score.

GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders

“…Supporting this finding are results showing that the GC1f genotype is associated with an augmented risk of chronic inflammatory diseases. Thus, (1) in chronic obstructive pulmonary disease (COPD), GCf1 was strongly associated with the risk of disease [ 55 ]; (2) in bronchiectasis, patients carrying the GC1f isoform have a more severe disease and more chronic infections in comparison with those without the GC1f isoform [ 56 ]; (3) in inflammatory bowel disease the GC2 isoform was less frequently observed in patients compared with healthy controls, suggesting a protective role [ 57 ]. On the other hand, the same GC2 isoform was associated with asthma susceptibility in the Chinese Han population [ 58 ].…”

Vitamin D in Health and Disease

“…RV has been shown to inhibit the profibrotic action of TGF-b1 in patients with pulmonary fibrosis [6,8]. Oriano et al [9] confirmed that VD-binding protein (DBP) polymorphisms and the resulting isoform are involved in the pathogenesis and severity of bronchiectasis, where DBP is coded by the GC gene. Notably, the GC1f isoform (rs7041/rs4588 A/G) correlated with a more severe disease, a higher incidence of chronic infections and a lower bronchiectasis etiology and comorbidity index (BACI) score.…”