Abstract
Several traits associated with asthma phenotypes, such as high total serum immunoglobulin E and bronchial hyperresponsiveness, have been linked by numerous genome-screen studies and linkage analyses to markers on human chromosome 5q31-q34. In the present article, we describe
UGRP1 (encoding uteroglobin-related protein 1) as one of asthma-susceptibility genes that is located on chromosome 5q31-q32. UGRP1 is a homodimeric secretory protein of 17 kDa and is expressed only in lung and trachea. The G→A polymorphism was identified at −112 bp in the human
UGRP1 gene promoter. The −112A allele is responsible for a 24% reduction in the promoter activity in relation to the −112G allele, as examined by transfection analysis. Electrophoretic mobility-shift analysis revealed that an unknown nuclear factor binds to the region around −112 bp. The binding affinity with the −112A oligonucleotide was reduced by approximately one half, as compared with the −112G oligonucleotide. In a case-control study using 169 Japanese individuals (84 patients with asthma and 85 healthy control individuals), those with a −112A allele (G/A or A/A) were 4.1 times more likely to have asthma than were those with the wild-type allele (G/G).
