Interleukin-10 and transforming growth factor-β promoter polymorphisms in allergies and asthma

K Hobbs, J Negri, M Klinnert… - American journal of …, 1998 - atsjournals.org
K Hobbs, J Negri, M Klinnert, LJ Rosenwasser, L Borish
American journal of respiratory and critical care medicine, 1998atsjournals.org
Interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) 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-β 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 …
Interleukin-10 (IL-10) and transforming growth factor beta (TGF- β ) 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- β 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- β gene promoters (3 in TGF- β 1 and 1 in TGF- β 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- β 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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