Association of group‐specific component exon 11 polymorphisms with bronchial asthma in children and adolescents

Several studies have investigated the association of Group‐specific Component (GC) gene, also known as vitamin D‐binding protein (VDBP), and various respiratory disorder susceptibility with conflicting results. In this sense, we aimed to investigate whether rs7041 and rs4588 variants confer susceptibility to bronchial asthma in a sample of an Egyptian population and to elucidate by in silico analysis the structural and functional impact of these variants. Group‐specific Component polymorphisms rs7041 and rs4588 were genotyped in 192 Egyptian children and adolescents (96 with asthma and 96 healthy controls) by TaqMan single nucleotide polymorphism genotyping assay. The rs7041 GG genotype showed a significantly elevated frequency among patients under codominant, dominant, recessive and allelic models where the patient group had greater carriage rate of G allele [OR 2.15, CI 95% (1.32‐3.50; P = 0.002)], while rs4588 CA and AA genotypes were found to be protective genotypes with controls showing a greater carriage rate of A allele [OR 0.52, CI 95% (0.30 ‐ 0.90; P = 0.02)]. Three haplotype allele combinations were identified with frequencies of GC (44.3%), TC (31.3%) and TA (24.5%) in the total study population. GC haplotype was shown to be more frequent in controls, while TC and TA haplotypes were more predominant in the patient group. Only rs7041 variant showed a significant association with family history and pubertal status. In conclusion, both study GC variants could be implicated in childhood bronchial asthma pathogenesis; rs7041 GG genotype and G allele increased asthma risk while rs4588 AA genotype and A allele conferred protection in the study population.     

Vitamin D binding protein and vitamin D in human allergen‐induced endobronchial inflammation

Allergic asthma is a chronic disease of the airways associated with airway hyperresponsiveness, a variable degree of airflow obstruction, airway remodelling and a characteristic airway inflammation. Factors of the vitamin D axis, which include vitamin D metabolites and vitamin D binding protein (VDBP), have been linked to asthma, but only few data exist about their regulation in the lung during acute allergen‐induced airway inflammation. Therefore, we analysed the regulation of factors of the vitamin D axis during the early‐ and late‐phase reaction of allergic asthma. Fifteen patients with mild allergic asthma underwent segmental allergen challenge. VDBP was analysed in bronchoalveolar lavage fluid (BALF) and serum using the enzyme‐linked immunosorbent assay (ELISA) technique. 25‐hydroxyvitamin D₃ [25(OH)D₃] and 1,25‐dihydroxyvitamin D₃ [1,25(OH)₂D₃] were analysed by a commercial laboratory using the liquid chromatography–mass spectrometry (LC/MS) technique. VDBP (median 2·3, range 0·2–7·1 μg/ml), 25(OH)D₃ (median 0·060, range < 0·002–3·210 ng/ml) and 1,25(OH)₂D₃ (median < 0·1, range < 0·1–2·8 pg/ml) were significantly elevated in BALF 24 h but not 10 min after allergen challenge. After correction for plasma leakage using the plasma marker protein albumin, VDBP and 25(OH)D₃ were still increased significantly while 1,25(OH)₂D₃ was not. VDBP and 25(OH)D₃ were correlated with each other and with the inflammatory response 24 h after allergen challenge. Serum concentrations of all three factors were not influenced by allergen challenge. In conclusion, we report a significant increase in VDBP and 25(OH)D₃ in human BALF 24 h after allergen challenge, suggesting a role for these factors in the asthmatic late‐phase reaction.     

Vitamin D binding protein gene polymorphisms and chronic obstructive pulmonary disease: a meta-analysis

Background

A number of polymorphisms in vitamin D binding protein (VDBP) (GC) gene have been implicated in risk of chronic obstructive pulmonary disease (COPD), but the results were controversial. GC1F, GC1S, and GC2 are three common variants of the VDBP gene [single nucleotide polymorphisms (SNPs): rs7041 and rs4588], which were reported to be associated with COPD. This study aimed to explore the association between VDBP gene polymorphisms and COPD.

Methods

PubMed, EMBASE, Web of Science (Medline) and Chinese National Knowledge Infrastructure (CNKI) were searched for eligible case-control studies. Study quality was evaluated using the Newcastle-ottawa quality assessment scale (NOS). After the most appreciated genetic model was identified, a meta-analysis was performed to test the association between VDBP gene polymorphism and COPD. The pooled odds ratios (ORs) were performed respectively for the most appreciated genetic model, single allele comparison and homozygous gene model analysis. Summary receiver operating characteristic curve (SROC) analyses were applied to evaluate the diagnostic performance of polymorphism of VDBP to COPD.

Results

Eight studies containing 2,216 participants were included. The analyses of the most appropriate genetic models offered significant results in recessive model of GC1F/1S group (OR =2.18), co-dominant genetic model in GC1F/2 group (1F-1F vs. 2-2: OR =4.87; 1F-2 vs. 2-2: OR =1.73; 1F-1F vs. 1F-2: OR =2.27). In single allele comparison, significant results were obtained in GC1F vs. GC1S and GC1F vs. GC2, with ORs were 1.47 and 1.77, respectively. In homozygous genes comparison, the OR was 2.51 in GC1F homozygote vs. other genotypes. Subgroup analyses offered the same significant results in Asian population, but not in Caucasian population. The SROC analyses showed the less accurate performance of polymorphism of VDBP to COPD.

Conclusions

There is a close association between COPD and GC gene polymorphisms. The GC1F allele could be a risk factor, the GC1S and GC2 allele may be protective factors in Asian, but not in Caucasians.     

Demonstration of vitamin D-binding protein (Gc-globulin) in the urine of Itai-itai disease patients

Vitamin D-binding protein (VDBP, known as Gc-globulin) was discovered by an immunochemical method in the urine of patients with Itai-itai disease. The urine and sera of Itai-itai disease patients produced specific precipitin lines with anti-human VDBP antisera. The electrophoretic mobility of the protein in the urine is the same as that in the serum. A significant correlation was found between VDBP and beta 2-microglobulin in the urine. Based on this result, it was concluded that Itai-itai disease is associated with disturbances of vitamin D transport and/or metabolism.     

Vitamin D‐binding protein polymorphisms are not associated with development of (multiple) basal cell carcinomas

Abstract: Vitamin D‐binding protein (VDBP) single nucleotide polymorphisms (SNP) may affect skin carcinogenesis. The objective was to test the association between two functional VDBP SNPs and the susceptibility to (multiple) basal cell carcinomas (BCCs). Of the 7983 participants, 5790 (72.5%) and 5823 (72.9%) participants were genotyped for rs7041 and rs4588, respectively, and three haplotypes (Gc1s, Gc2 and Gc1f) were analysed. Two hundred and thirty‐three persons developed a BCC of whom 122 (52.4%) developed multiple BCCs during a mean follow‐up of 11.6 years. The VDBP genotype was not associated with (multiple) BCC development using Cox proportional hazards and Andersen‐Gill analyses, respectively. Stratifying age groups demonstrated that in the youngest age‐group, the A/T variant of rs7041 was associated with BCC development [adjusted hazard ratio (HR) = 1.88 (95%CI 1.10–3.20)], while homozygote Gc1s carriers had a significantly lower BCC risk [adjusted HR = 0.53 (95%CI 0.31–0.91)]. In conclusion, the VDBP polymorphisms were not associated with susceptibility to (multiple) BCCs, but age–gene interactions were observed.     

Vitamin D binding protein,but not vitamin D or vitamin D-related peptides,is associated with septic shock mortality

Background

The aim of this study was to assess the prognostic value of vitamin D, vitamin D binding protein (VDBP) and vitamin D-related peptides in septic shock patients in relation to hospital mortality.