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Microsatellite DNA instability and loss of heterozygosity in bronchial asthma

Dept of Thoracic Medicine and Laboratory of Virology, Medical School, University of Crete, Greece

CORRESPONDENCE: N.M. Siafakas, Dept of Thoracic Medicine, University General Hospital, 71110 Heraklion, Crete, Greece. Fax: 30 2810542650. E-mail: siafak@med.uoc.gr

Keywords: atopy, deoxyribonucleic acid alterations, genetic susceptibility, human genome, hyperresponsiveness, induced sputum

Received: January 30, 2003
Accepted July 14, 2003

Genetic alterations, such as loss of heterozygosity (LOH) or microsatellite instability (MI), have been reported in both malignant and benign disorders. In order to identify loci of deoxyribonucleic acid (DNA) mutation in asthma, MI and LOH were studied in sputum cells.

DNA was extracted from cells in the sputum and blood cells of 22 patients with moderate asthma. Cells were analysed for MI and LOH using 18 polymorphic markers on chromosome 5q, 6p, 11q, 14q. Microsatellite analysis was also performed in six healthy subjects.

None of the healthy individuals exhibited any genetic alteration. Genetic alterations were found in 16 of 22 asthmatic patients (73%). In total, 12 (54.5%) patients exhibited LOH only, one (4.5%) MI only, while three showed both MI and LOH. The highest incidence of LOH and MI was found on chromosome 14q. Mean immunoglobulin E and blood eosinophil levels were significantly higher in asthmatics with three or more genetic alterations.

A high incidence of genetic alterations in the deoxyribonucleic acid of the sputum cells was found in asthmatic patients. Further studies are needed to identify the role of loss of heterozygosity and microsatellite instability in the investigation of genetic susceptibility of asthma and thus, in its pathogenesis.

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