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Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1958-1962

Interleukin-10 and Transforming Growth Factor-beta Promoter Polymorphisms in Allergies and Asthma

KATHRYN HOBBS, JULIE NEGRI, MARY KLINNERT, LANNY J. ROSENWASSER, and LARRY BORISH

Departments of Medicine and Pediatrics, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado

Interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta ) are inhibitory for B and T cells, IgE production, and mast cell proliferation, and they induce apoptosis in eosinophils. These cytokines are therefore candidate genes which could contribute to the development of asthma or allergies. We investigated the hypothesis that polymorphic nucleotides within the IL-10 and TGF-beta gene promoters would link to the expression of allergies and asthma. DNA taken from families with an asthmatic proband was examined for base exchanges by single-stranded conformational polymorphism (SSCP). We demonstrated the presence of a polymorphism in the promoter region of the IL-10 gene and four in the TGF-beta gene promoters (3 in TGF-beta 1 and 1 in TGF-beta 2). The IL-10 gene polymorphism was a C-to-A exchange 571 base pairs upstream from the translation start site and was present between consensus binding sequences for Sp1 and elevated total serum. This polymorphism was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange (p < 0.009). The base exchange at -509 (from the transcription initiation site) in the TGF-beta promoter also linked to elevated total IgE (p < 0.01). This polymorphism represented a C-to-T base exchange which induced a YY1 consensus sequence and is present in a region of the promoter associated with negative transcription regulation.




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