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).
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Authors | Tomoaki Niimi, Mitsuru Munakata, Catherine L Keck-Waggoner, Nicholas C Popescu, Roy C Levitt, Michie Hisada, Shioko Kimura |
Journal | American journal of human genetics
(Am J Hum Genet)
Vol. 70
Issue 3
Pg. 718-25
(Mar 2002)
ISSN: 0002-9297 [Print] United States |
PMID | 11813133
(Publication Type: Journal Article)
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Chemical References |
- Carrier Proteins
- DNA-Binding Proteins
- Nuclear Proteins
- SCGB3A2 protein, human
- Secretoglobins
- Transcription Factors
- Immunoglobulin E
- DNA
- Uteroglobin
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Topics |
- Alleles
- Asthma
(genetics, immunology)
- Base Sequence
- Carrier Proteins
- Case-Control Studies
- Chromosomes, Human, Pair 5
(genetics)
- DNA
(genetics, metabolism)
- DNA-Binding Proteins
(metabolism)
- Electrophoretic Mobility Shift Assay
- Exons
(genetics)
- Gene Expression Regulation
- Gene Frequency
- Genetic Predisposition to Disease
- Humans
- Immunoglobulin E
(blood)
- In Situ Hybridization, Fluorescence
- Introns
(genetics)
- Japan
- Molecular Sequence Data
- Nuclear Proteins
(metabolism)
- Polymorphism, Genetic
(genetics)
- Promoter Regions, Genetic
(genetics)
- Secretoglobins
- Substrate Specificity
- Transcription Factors
(genetics)
- Transcription, Genetic
(genetics)
- Uteroglobin
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