title: The TNF (-308A) polymorphism is associated with microchimerism in transfused trauma patients.
abstract: 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 after transfusion of trauma patients. We used 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 4 functionally significant SNPs: TNF (-308), IL 10 (-1082), IFNG (+874), and TGFB1 (+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.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Gill
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Garth H
authors.initials: GH
authors.lastname: Utter
authors.forename: William F
authors.initials: WF
authors.lastname: Reed
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Dan
authors.initials: D
authors.lastname: Chafets
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D001803:Blood Transfusion; D046528:Chimerism; D005260:Female; D005838:Genotype; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D014947:Wounds and Injuries / Q000235:genetics* / Q000276:immunology / Q000628:therapy
chemical_list: C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma