Bronchial asthma is a complex, inflammatory disorder of the airways characterized by variable airflow obstruction with airway hyperresponsiveness. Asthma-associated phenotypes include bronchial hyperresponsiveness and atopy. A number of genetic studies have identified multiple chromosomal regions that contribute to the development of asthma and asthma-associated phenotypes. We have identified Uteroglobin-related protein (UGRP) 1 that is a novel secreted protein with an amino acid sequence similar to Uteroglobin (UG)/Clara cell secretory protein (CCSP). UG/CCSP is known to have a cytokine-like function, and genetic polymorphisms of the gene have been associated with susceptibility to asthma. Molecular biological, biochemical, histological, and immunological characterization of mouse and human UGRP1 and their genes suggested that UGRP1 appears to play a role in lung inflammation and is a plausible asthma susceptible gene. A single nucleotide polymorphism (SNP) was identified in the human UGRP1 gene promoter that is responsible for reduced transcriptional activity of the gene due to lower affinity of a particular nuclear protein to the binding site around the polymorphic site. This results in alteration of the concentration or activity of the UGRP1 protein, which may ultimately contribute to the development of clinical asthma. A case-control study demonstrated the association between this SNP and an increased risk of asthma among Japanese subjects. Studies are under way to determine the role of UGRP1 in lung inflammation.
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