Interleukin-6 Receptor Polymorphism Is Prevalent in HIV-negative Castleman Disease and Is Associated with Increased Soluble Interleukin-6 Receptor Levels |
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| Authors: | Katie Stone Emily Woods Susann M. Szmania Owen W. Stephens Tarun K. Garg Bart Barlogie John D. Shaughnessy Jr Brett Hall Manjula Reddy Antje Hoering Emily Hansen Frits van Rhee |
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| Affiliation: | 1. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.; 2. Signal Genetics, LLC., New York, New York, United States of America.; 3. Janssen Research and Development, Radnor, Pennsylvania, United States of America.; 4. Cancer Research and Biostatistics, Seattle, Washington, United States of America.; Baylor College of Medicine, United States of America, |
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| Abstract: | Multicentric Castleman Disease is largely driven by increased signaling in the pathway for the plasma cell growth factor interleukin-6. We hypothesized that interleukin-6/interleukin-6 receptor/gp130 polymorphisms contribute to increased interleukin-6 and/or other components of the interleukin-6 signaling pathway in HIV-negative Castleman Disease patients. The study group was composed of 58 patients and 50 healthy donors of a similar racial/ethnic profile. Of seven polymorphisms chosen for analysis, we observed an increased frequency between patients and controls of the minor allele of interleukin-6 receptor polymorphism rs4537545, which is in linkage disequilibrium with interleukin-6 receptor polymorphism rs2228145. Further, individuals possessing at least one copy of the minor allele of either polymorphism expressed higher levels of soluble interleukin-6 receptor. These elevated interleukin-6 receptor levels may contribute to increased interleukin-6 activity through the trans-signaling pathway. These data suggest that interleukin-6 receptor polymorphism may be a contributing factor in Castleman Disease, and further research is warranted. |
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