Expression profiling of major histocompatibility and natural killer complex genes reveals candidates for controlling risk of XXXX .

@entity1 @entity56113 @entity4493 @entity3173 @entity11654 @entity2132 @entity272 @entity35
BACKGROUND: The @entity3173 ( @entity3173 ) is the most important genomic region that contributes to the risk of @entity2132 ( @entity2132 ) after haematopoietic stem cell transplantation. Matching of @entity3173 class I and II genes is essential for the success of transplantation. However, the @entity3173 contains additional genes that also contribute to the risk of developing acute @entity2132 . It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify @entity3173 genes and other genes involved in the pathophysiology of @entity2132 by mRNA expression profiling. METHODOLOGY/PRINCIPAL FINDINGS: To reduce the complexity of the task, we used genetically well-defined @entity35 inbred strains and a @entity35 skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR), to analyze the expression of @entity3173 , natural killer complex (NKC), and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 @entity3173 , 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected @entity3173 and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in @entity2132 -affected @entity272 of transplanted @entity35 and in @entity1 skin explant assays. CONCLUSIONS/SIGNIFICANCE: We identified @entity35 and @entity1 @entity3173 and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for @entity2132 . Several of the respective @entity1 genes, including HLA-DMB, C2, @entity11654 , @entity56113 , UBD, and @entity4493 , are polymorphic. These candidates may therefore contribute to the genetic risk of @entity2132 in @entity1 .
