A polymorphism in the human UGRP1 gene promoter that regulates transcription is associated with an increased risk of asthma.
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).
Niimi
Tomoaki
T
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Munakata
Mitsuru
M
Keck-Waggoner
Catherine L
CL
Popescu
Nicholas C
NC
Levitt
Roy C
RC
Hisada
Michie
M
Kimura
Shioko
S
D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D002352:Carrier Proteins; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D007564:Japan; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D060765:Secretoglobins; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D014598:Uteroglobin
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C449940:SCGB3A2 protein, human; D060765:Secretoglobins; D014157:Transcription Factors; D007073:Immunoglobulin E; D004247:DNA; D014598:Uteroglobin