Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02774 (Gc-globulin)
 196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gc-globulin has been found in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease (COPD) and adult respiratory distress syndrome (ARDS) and has been shown to enhance neutrophil chemotaxis to C5-derived peptides in vitro. We proposed that Gc-globulin may enhance the inflammatory response in lungs by influencing monocyte chemotaxis to C5-derived peptides as it does with neutrophils. Monocyte chemotaxis was measured in blind well chambers by a leading-front technique. Purified human Gc-globulin had no intrinsic chemotactic activity for monocytes at concentrations ranging from 1 fM to 1 microM. However, Gc-globulin, at concentrations as low as 10 pM, increased monocyte chemotaxis over 10-fold in a concentration-dependent fashion when added to non-chemotactic doses of C5a (0.1 nM) and C5a des Arg (0.5 nM). The chemotaxis-enhancing effect of Gc-globulin was specific for C5-derived peptides, as Gc-globulin did not enhance monocyte chemotaxis to other chemoattractants such as leukotriene B4 or formyl-Met-Leu-Phe. The enhancement of monocyte chemotaxis to C5-derived peptides by Gc-globulin was not a nonspecific effect of anionic proteins, as other serum proteins of similar size and charge did not enhance monocyte chemotaxis to C5a des Arg. These results indicate that Gc-globulin enhances the monocyte response to C5-derived peptides and, together with previous work, indicates that its presence in the airways of patients with COPD and ARDS may up-regulate the monocyte inflammatory response in the lungs.
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PMID:Human monocyte chemotaxis to complement-derived chemotaxins is enhanced by Gc-globulin. 812 Apr 52

Although the development of chronic obstructive pulmonary disease (COPD) in smokers shows genetic susceptibility, only alpha1-antitrypsin deficiency has been identified as a definite genetic risk factor. There have been three previous studies in which associations between Gc-globulin phenotypes and COPD have been investigated. Although some data suggest an association, the results were inconclusive. Because smoking is the major risk factor for COPD, it may have been a confounding factor in previous studies. We have investigated Gc-globulin genotypic frequencies among 75 COPD patients and 64 nonobstructed controls. Both groups had significant smoking histories: pack-years (mean +/- SD) of 52 +/- 30 and 48 +/- 27, respectively. The results show that homozygosity for the Gc2 allele is protective against COPD (OR = 0.17, 95% CI = 0.03 to 0.83). There were no differences between genotypes for lung elastic recoil values or for the level of upstream airway resistance. Gc-globulin can enhance complement (C5a)-mediated neutrophil chemotaxis. Because neutrophils play a role in parenchymal destruction and airway inflammation, we examined whether Gc-globulin's ability to enhance neutrophil chemotaxis varied with genotype. We found no difference among genotypes with respect to neutrophil chemotaxis suggesting that the protective effect of the Gc2 allele is mediated through a different mechanism.
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PMID:Vitamin D binding protein variants and the risk of COPD. 951 17

Chronic obstructive pulmonary disease (COPD) and diffuse panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and-control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% versus control 20.7%), and the odds ratio for GC*IF homozygotes was 2.2 (95%, confidence interval 1.1-4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozvgotes, GC*2-1F heterozygotes, GC*2-1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*IF gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to diffuse panbronchiolitis was found.
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PMID:Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis. 1175 23

The distribution of alleles and genotypes of vitamin D-binding protein (DBP) gene has been studied in patients with Chronic Obstructive Pulmonary Disease (COPD, n = 298) and healthy individuals (n = 237) from two ethnic groups (Tatars and Russians) living in Republic Bashkortostan. Statistically significant differences in the distribution of DBP gene genotypes between Tatars and Russians (chi2 = 8.854, df = 5, P = 0.04) were revealed. The pattern of allele's distribution within DBP gene was similar in healthy control subjects of both ethnic groups, with gradient reduction in row GC*1S> GC*1F> GC*2. The most common genotypes were: GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It has been shown, that Tatars with genotype GC*1F/1S have a lower risk of COPD development: the frequency of GC*1F/1S genotype in COPD patients was significantly lower than in healthy individuals (19.85% versus 36.79%; chi2 = 7.622, P = 0.0067, Pcor = 0.0335; OR = 0.42 CI 95% 0.22-0.79). At the same time, COPD patients from the same group had higher frequency of GC* 1F/2 genotype than healthy individuals (19.08% versus 8.49%; chi2 = 4.52, P = 0.033, Pcor = 0.165; OR = 2.54 CI 95% 1.067-6.20). In Russian population the distribution of alleles and genotypes of DBP gene were similar in COPD patients and healthy individuals.
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PMID:[Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan]. 1663 63

Gc-globulin is a multifunctional glycoprotein with a molecular mass of 51-58 kDa. It is also called vitamin D-binding protein (DBP). The main function of Gc-globulin is to bind vitamin D and actin, which is released into the extracellular environment upon cell and tissue lysis. Gc-globulin appears to have important clinical significance. Some investigation have shown that a low concentration of Gc-globulin may be used as a prognostic factor in patients with fulminant hepatic failure, acetaminophen (paracetamol) overdose, multiple trauma or multiple organ dysfunction syndrome (MODS), or sepsis. Many studies suggest an association between Gc-globulin phenotypes and resistance or susceptibility to chronic obstructive pulmonary disease (COPD), thyroid diseases, diabetes, multiple sclerosis, and sarcoidosis.
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PMID:[The significance of Gc-globulin in clinical practice]. 1900 85

There has been much recent interest in the role of the vitamin D axis in lung disease, which includes vitamin D, vitamin D receptor (VDR) and vitamin D-binding protein (VDBP; also known as Gc-globulin). VDBP is a serum protein which has immunomodulatory functions relevant in the lung, predominantly relating to macrophage activation and neutrophil chemotaxis. Variations within its gene are also associated with airways disease, implying a role for the protein product in pathogenesis. Thus far the majority of evidence relates to chronic obstructive pulmonary disease (COPD), but is scant in other airways diseases, such as asthma and bronchiectasis. VDBP also acts as a scavenger protein to clear extracellular G-actin released from necrotic cells, which may be of relevance in severe lung infections and acute lung injury. Vitamin D protects against the development of cancer and tuberculosis, although optimal levels are unknown. The majority of circulating vitamin D is bound to VDBP, and its uptake into cells occurs in both bound and unbound forms, which suggests the role of VDBP warrants further study in these conditions as well. This article reviews the evidence of the role VDBP and its gene (GC) in a range of lung diseases, including asthma, COPD and tuberculosis.
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PMID:The vitamin D axis in the lung: a key role for vitamin D-binding protein. 2043 72

Chronic obstructive pulmonary disease (COPD) is not fully recognized process regarding many risk factors genetics and environmental. Etiology of COPD is not fully understood. There is evidence of a hereditary component in COPD. Patients with hereditary alpha1-antitrypsin deficiency are at risk of developing COPD. A number of genetic association studies have been performed to find susceptibility genes of COPD. Many of genes play an important role in development of COPD. This review examines the impact of alpha1-antitrypsin, matrix metalloproteinases, tumour necrosis factor gene a, microsomal epoxide hydrolase, transforming growth factor b-1, Vitamin D-binding protein and CFTR on COPD extension.
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PMID:[Genetics risk factors in chronic obstructive pulmonary disease]. 2049 42

The vitamin D-binding protein (VDBP) genetic polymorphisms have been associated with chronic obstructive pulmonary disease (COPD). A number of studies have been conducted to investigate the combined effects of the VDBP gene (GC) rs7041 and rs4588 polymorphisms on the COPD risk. However, the results obtained are inconclusive. The present meta-analysis aimed to investigate whether GC polymorphisms may be a potential risk factor for COPD. The Web of Science, PubMed, Google Scholar, Embase, Cochrane Library, China National Knowledge Infrastructure and Wanfang Database were searched from inception until June 1, 2014. The meta-analysis was performed using the STATA 12.0 software. Twelve case-control studies, including 2,937 subjects, met the inclusion criteria. Overall, a significantly increased risk was detected in populations of GC*1F homozygotes, whereas no associations between other GC polymorphisms and COPD risk were detected. According to ethnicity, the results demonstrated that the GC*1F homozygotes may be a risk factor for COPD and the GC*2 homozygotes may be a protective factor against COPD in the Asian population. However, similar associations were not observed among the Caucasian population. In conclusion, the current meta-analysis indicates that the GC*1F homozygotes may be a risk factor for COPD and the GC*2 homozygotes may be a protective factors against COPD in the Asian population.
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PMID:Vitamin D-binding protein gene polymorphisms and chronic obstructive pulmonary disease susceptibility: A meta-analysis. 2579 46

Vitamin D-binding protein (DBP), a highly polymorphic serum protein, encoded by GC gene, is important in the development of chronic obstructive pulmonary disease (COPD). This meta-analysis was performed to assess the association between GC polymorphisms (1F, 1S, and 2 alleles) and COPD susceptibility. Published case-control studies were retrieved from the Pubmed, Embase, and China National Knowledge Infrastructure databases. After data extraction, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Seven case-control studies were included. Pooled effect size showed that GC polymorphisms were not significantly associated with COPD susceptibility. According to ethnicity, the 1F allele was significantly correlated with COPD susceptibility in Asians (1F vs 1S, OR: 1.52, 95%CI: 1.16-2.00 and 1F vs 2, OR: 1.87, 95%CI: 1.42-2.44), indicating that individuals with the 1F allele have an increased risk of COPD compared to those with the 1S or 2 allele. However, the 1F allele was associated with a lower, insignificant risk of COPD than the 1S and 2 alleles in Caucasians (1F vs 1S, OR: 0.83, 95%CI: 0.64-1.08 and 1F vs 2, OR: 0.73, 95%CI: 0.54-0.98). Moreover, no significant association was found for the 1S and 2 alleles in Asians (OR: 1.23, 95%CI: 0.90- 1.69) and Caucasians (OR: 0.89, 95%CI: 0.70-1.13). After excluding each study, the pooled results were robust and no publication bias was observed. We found that the GC 1F allele confers a risk of COPD in Asians, whereas the 1F allele may protect against COPD in Caucasians.
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PMID:Dual role of vitamin D-binding protein 1F allele in chronic obstructive pulmonary disease susceptibility: a meta-analysis. 2596 20

Gene polymorphism of vitamin D-binding protein (VDBP) correlates with chronic obstructive pulmonary disease (COPD), but the results remain inconclusive. We aimed to explore the association between VDBP gene polymorphism and COPD. We searched MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure for publications addressing the association between VDBP gene polymorphism and COPD. After qualitative evaluation, randomized controlled trials were pooled using either a fixed- or a random-effect model depending upon the degree of heterogeneity. Eleven studies with 3144 subjects were included. The genotype group-specific component (GC)*1F-1F was significantly associated with COPD in Asians [odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.07-2.81, P = 0.03], but not in Caucasians (OR = 1.44, 95%CI = 0.57-3.66, P = 0.45). A protective effect of GC*1F-1S was observed in Asians (OR = 0.70, 95%CI = 0.55-0.89, P = 0.003) but not in Caucasians (OR = 0.93, 95%CI = 0.69-1.24, P = 0.61). There was no association of GC*1S-1S, GC*2-1S and GC*1F-2 with COPD. As for alleles, GC*1F was a risk factor, whereas GC*1S was protective against COPD in Asians; GC*2 was not protective. The genotype GC*1F-1F or allele GC*1F was associated with increased susceptibility to COPD in Asians. No protective effect of genotype GC*2-2 against COPD was found. The protective effects of GC*1F-1S and GC*1S were observed in Asians but not in Caucasians. The VDBP gene polymorphism could be a potential marker for screening of COPD.
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PMID:Association of vitamin D-binding protein variants with chronic obstructive pulmonary disease: a meta-analysis. 2640 Mar 6


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