Submitted August 21, 2007
Accepted January 10, 2008
The TNF
-308A polymorphism is associated with microchimerism in transfused
trauma patients
Ryan M Gill, Tzong-Hae Lee, Garth H. Utter, William F Reed, Li Wen, Dan Chafets, and Michael P Busch*
Department of Laboratory Medicine, University of California, San Francisco, Ca, United States
Blood Systems Research Institute, BSRI, San Francisco, Ca, United States
Department of Surgery, University of California, Davis, Ca, United States
* Corresponding author; email: mbusch{at}bloodsystems.org.
Microchimerism (MC), defined as the persistence of allogeneic cells at low concentrations, is well documented in transfused trauma patients. We hypothesized that genetic polymorphisms linked to cytokine production could contribute to trauma-induced immune modulation and development of microchimerism following transfusion of trauma patients. We utilized high-throughput SYBR-green-based genotyping of single nucleotide polymorphisms (SNPs) to characterize 59 transfused trauma patients, with MC (n=30) and without MC (n=29), for four functionally significant SNPs: TNF
(-308), IL10(-1082), IFN
(+874) and TGF
1(+915). We then compared likelihood for development of MC and the magnitude of immune suppression among subjects with and without these selected immune response SNPs. We identified a significant association between TNF(-308A) SNP and both development of MC and diminished immune responsiveness. Hence predisposing genetic factors may explain, in part, why only a subset of trauma patients develops transfusion-associated microchimerism.
