Plasma UGRP1 Levels Associate with Promoter G-112A Polymorphism and the Severity of Asthma

Inoue, Keiichi; Wang, Xintao; Saito, Junpei; Tanino, Yoshinori; Ishida, Takashi; Iwaki, Daisuke; Fujita, Teizo; Kimura, Shioko; Munakata, Mitsuru

doi:10.2332/allergolint.o-07-493

Cited by 19 publications

(23 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed reduced levels of serum UGRP1 in carriers homozygous for A/A, which is consistent with the results of other studies that found association between the carriage of the SCGB3A2 −112A variant and lower levels of either SCGB3A2 expression (Niimi et al 2002, Song et al 2009 or serum UGRP1 (Inoue et al 2008). A guanine-to-adenine substitution at position −112 of the SCGB3A2 promoter disrupts the sequence of the binding site for CCAAT/ enhancer-binding protein α (C/EBPα), a positive regulator of the transcription of SCGB3A2 Song et al 2009).…”

Section: Discussionsupporting

confidence: 94%

“…Similarly, Inoue et al (2008) found elevated concentrations of this protein in mild asthma but two-fold decreased UGRP1 levels in severe asthma in comparison with the controls. In the murine model of allergic airway inflammation, UGRP1 was reported to inhibit lung inflammation (Chiba et al 2006).…”

Section: Discussionmentioning

confidence: 88%

“…However, the association between this variant of SCGB3A2 and asthma was further replicated neither in Japanese (Jian et al 2003;Inoue et al 2008) nor in Caucasians (Heinzmann et al 2003;Batra et al 2005;Rigoli et al 2007). Despite an obvious lack of association with asthma, this promoter polymorphism of SCGB3A2 was shown to influence the transcription of SCGB3A2 (Niimi et al 2002) and modulate the severity of asthma (Inoue et al 2008).…”

Section: Discussionmentioning

confidence: 96%

“…Using a TaqMan allele discrimination assay, the marker rs1368408 was genotyped on an ABI 7500 Fast Real-Time PCR machine (Applied Biosystems, Foster City, CA, USA), as described by Inoue et al (2008). In the TaqMan assay, a calling rate was 98.5%.…”

Section: Dna Analysismentioning

confidence: 99%

See 3 more Smart Citations

The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

et al. 2010

View full text Add to dashboard Cite

The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a susceptibility locus to several autoimmune and inflammatory diseases, including asthma and Graves' disease (GD). Recently, association between the marker rs1368408 (-112G >A), located in the promoter region of the SCGB3A2 gene, and susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to evaluate whether this polymorphism confers GD susceptibility in a large population cohort comprising 1,474 Russian GD patients and 1,619 controls. The marker rs1368408 was studied using a TaqMan allele discrimination assay. Serum levels of UGRP1 and immunoglobulin E (IgE) were assessed using enzyme-linked immunosorbent assay (ELISA) analyses. Association between the allele A of SCGB3A2 and a higher risk of GD (odds ratio [OR] = 1.33, P = 2.9 × 10(-5)) was shown. Both affected and non-affected carriers of the higher risk genotype A/A had significantly decreased levels of serum UGRP1 compared to the subjects homozygous for G/G (93 ± 37 pg/ml vs. 132 ± 45 pg/ml, P = 0.0011 for GD patients; 77 ± 28 pg/ml vs. 119 ± 33 pg/ml, P = 0.0019 for controls). Serum IgE levels were significantly higher in non-affected subjects homozygous for A/A compared to control individuals homozygous for G/G (153 ± 46 IU/ml vs. 122 ± 40 IU/ml, P = 0.0095). Our data suggest that the carriage of the SCGB3A2 -112A/A variant increases the risk for GD in subsets of patients with elevated levels of IgE, a hallmark of allergic asthma. Therefore, the SCGB3A2 -112G >A polymorphism may be considered as a likely marker linking susceptibility to allergy/asthma and GD on chromosome 5q31-33.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 96%

Section: Dna Analysismentioning

confidence: 99%

See 2 more Smart Citations

The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Furthermore, we do not know whether endogenous SCGB3A2 regulates pulmonary inflammation and/or fibrosis. However, the following evidence suggests a role for SCGB3A2 in inflammation in lung in vivo; in the ovalbumin-induced allergic airway inflammation model mouse, SCGB3A2 expression is reduced in the airways (24,48,49), and the plasma SCGB3A2 levels are significantly lower in severe asthmatics without oral corticosteroid treatment as compared with mild-or moderate-asthma patients and controls (50). In the current study, a rather strong focal SCGB3A2 expression was found in a part of epithelial cells, and overexpressed SCGB3A2 was accumulated in fibrotic foci of lungs of mice subjected to BLM.…”

Section: Discussionmentioning

confidence: 99%

Secretoglobin 3A2 Suppresses Bleomycin-induced Pulmonary Fibrosis by Transforming Growth Factor β Signaling Down-regulation

Kurotani

Okumura

Matsubara

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

With increasing worldwide rates of morbidity and mortality of pulmonary fibrosis, the development of effective therapeutics for this disease is of great interest. Secretoglobin (SCGB) 3A2, a novel cytokine-like molecule predominantly expressed in pulmonary airways epithelium, exhibits anti-inflammatory and growth factor activities. In the current study SCGB3A2 was found to inhibit TGF␤-induced differentiation of fibroblasts to myofibroblasts, a hallmark of the fibrogenic process, using pulmonary fibroblasts isolated from adult mice. This induction was through increased phosphorylation of STAT1 and expression of SMAD7 and decreased phosphorylation of SMAD2 and SMAD3. To demonstrate the effect of SCGB3A2 on the TGF␤ signaling in vivo, a bleomycin-induced pulmonary fibrosis mouse model was used. Mice were administered bleomycin intratracheally followed by intravenous injection of recombinant SCGB3A2. Histological examination in conjunction with inflammatory cell counts in bronchoalveolar lavage fluids demonstrated that SCGB3A2 suppressed bleomycin-induced pulmonary fibrosis. Microarray analysis was carried out using RNAs from lungs of bleomycin-treated mice with or without SCGB3A2 and normal mice treated with SCGB3A2. The results demonstrated that SCGB3A2 affects TGF␤ signaling and reduces the expression of genes involved in fibrosis. This study suggests the potential utility of SCGB3A2 for targeting TGF␤ signaling in the treatment of pulmonary fibrosis.

show abstract

Uteroglobulin‐related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital

Hashimoto

Katayose

Sakuma

et al. 2011

Journal of Medical Virology

Self Cite

View full text Add to dashboard Cite

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.

show abstract

Plasma UGRP1 Levels Associate with Promoter G-112A Polymorphism and the Severity of Asthma

Abstract: The ELISA system for quantifying UGRP1 protein was established, and plasma UGRP1 levels were associated with the G-112A UGRP1 gene promoter polymorphism and the severity of asthma.

Cited by 19 publications

References 35 publications

The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

Secretoglobin 3A2 Suppresses Bleomycin-induced Pulmonary Fibrosis by Transforming Growth Factor β Signaling Down-regulation

Uteroglobulin‐related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital

Contact Info

Product

Resources

About