Plasma UGRP1 levels associate with promoter G-112A polymorphism and the severity of asthma

Abstract

Background: Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways and is speculated to have anti-inflammatory activity. In the mouse, its gene expression is down-regulated by interleukin (IL)-5 and -9, and up-regulated by IL-10. However, the precise role of UGRP1 in human inflammatory airway diseases such as asthma has not been clarified. The objectives of this study were to establish an ELISA system to quantify UGRP1 protein, and to examine whether plasma UGRP1 levels are associated with the G-112A polymorphism, asthma susceptibility, and its severity.

Methods: 152 asthma patients and 103 normal controls were involved in this study. Mice were immunized with recombinant UGRP1 and hybridoma cell lines were established. A sandwich ELISA system was established by using two monoclonal antibodies recognizing different epitopes. Plasma UGRP1 levels were measured with the ELISA system and the G-112A allele was detected by using real-time PCR.

Results: An ELISA system was established that allowed determination of UGRP1 levels within the range of 9.6-1250 pg/ml. The mean plasma UGRP1 levels for subjects with -112A allele were significantly lower than those without it (p = 0.025). Although there was no significant difference in the plasma UGRP1 levels between asthma patients and controls (p = 0.13), severe asthma patients without oral corticosteroid had significantly lower plasma UGRP1 levels compared to mild- or moderate- asthma patients and controls (p = 0.004, 0.03 and 0.003, respectively).

Conclusions: 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.

Fig. 1

The standard curve (log-log fit) for measuring UGRP1 levels. UGRP1 concentration can be accurately determined between 9.6–1250 pg/ml.

Fig. 2

Comparison of plasma UGRP1 levels between subjects with (G/A or A/A) and without (G/G) -112A allele. The results for control subjects are shown. The total number of subjects with -112A allele was 37 and those without A allele was 66. Data are means +/− SE. * p = 0.02 compared to control.

Fig. 3

Comparison of plasma UGRP1 levels between control and asthma patients. Data are means +/− SE. There was no statistically significant difference.

Fig. 4

Comparison of plasma UGRP1 levels among healthy control and mild-severe asthmatic with or without oral corticosteroid (OS). Data are means +/− SE. ** p < 0.05 compared to control, mild, and moderate asthma. † p = 0.013 compared to severe asthma with OS.