Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6 receptor levels.
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.
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Katie
K
Stone
Emily
E
Woods
Susann M
SM
Szmania
Owen W
OW
Stephens
Tarun K
TK
Garg
Bart
B
Barlogie
John D
JD
Shaughnessy
Brett
B
Hall
Manjula
M
Reddy
Antje
A
Hoering
Emily
E
Hansen
Frits
F
van Rhee
D000483:Alleles; D016022:Case-Control Studies; D005871:Castleman Disease / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics* / Q000378:metabolism*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6