Interleukin-10 gene promoter polymorphisms in multiple myeloma

Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulati on of malignant plasma cells in the bone marrow. It is unclear whether gene tic background could have an etiological impact on MM or influence the cour se of the disease. Interleukin-10 (IL-10) has been implicated in the growth and differentiation of normal B cells, and has also been shown to enhance the proliferation of MM cells. To address the putative involvement of IL-10 genetic variation in MM, we analyzed previously defined loci for bi-alleli c polymorphism at position -1082 and two microsatellite loci (IL10.G and IL 10.R) in the IL-10 promoter region. Seventy-three patients with MM, 27 with monoclonal gammopathy of undetermined significance, and 109 ethnically mat ched individuals as controls were included in the study, Significantly incr eased frequencies of the IL10.G genotype 136/136 and the IL10.R genotype 11 2/114, in addition to a decreased frequency of the IL10.R genotype 114/116, were found among the MM patients. Increased production of IL-10 was detect ed in the supernatants of lipopolysaccharide-stimulated peripheral blood mo nonuclear cells from MM patients who were homozygotes (136/136) and heteroz ygotes (136/non-136) for the IL10.G allele 136, as compared with the other IL10.G genotype carriers (non-136/non-136). These results suggest that the genetic variation in the IL-10 promoter region may play a role in the devel opment of MM, (C) 2001 Wiley-Liss, Inc.