Association of the Q576R polymorphism in the interleukin-4 receptor alpha chain with indolent mastocytosis limited to the skin

Gain-of-function mutations in c-kit, which appear to contribute to mast cel l hyperplasia, have been detected in both limited and aggressive forms of m astocytosis, suggesting that other mutations or polymorphisms may contribut e to the clinical phenotype. Because addition of interleukin-4 (IL-4) to ma st cell cultures Is reported to induce apoptosis, the hypothesis was consid ered that individuals carrying the gal n-of-function polymorphism Q576R in the cytoplasmic domain of the alpha -subunit of the IL-4 receptor (IL-4R) m ight be relatively resistant to the gain-of-function mutation In c-kit. To assess this possibility, 36 patients with either cutaneous or systemic mast ocytosis were studied for association with the Q576R polymorphism. The 0576 R polymorphism was found more frequently in those with disease limited to s kin and who exhibited lower levels of surrogate disease markers. These data suggest that the Q576R IL-4R alpha- chain polymorphism may mitigate diseas e expression and confer a better prognosis in patients with mastocytosis. ( C) 2001 by The American Society of Hematology.