A polymorphism in the human UGRP1 gene promoter that regulates transcription is associated with an increased risk of asthma

Tomoaki Niimi, Mitsuru Munakata, Catherine L. Keck-Waggoner, Nicholas C. Popescu, Roy C. Levitt, Michie Hisada, Shioko Kimura

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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).

Original languageEnglish (US)
Pages (from-to)718-725
Number of pages8
JournalAmerican journal of human genetics
Volume70
Issue number3
DOIs
StatePublished - Mar 2002

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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