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Chunk #3 — Background

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Complex nature of SNP genotype effects on gene expression in primary human leucocytes.
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Here we present an association based genetical genomics study using primary cell RNA from peripheral blood sampled from patients in remission from an immune-mediated disease. Immediate RNA preservation during blood sampling (using the PAXgene system) represents nearly in vivo human physiological gene expression. Celiac disease is a common (1% prevalence), inflammatory condition of the small intestine induced by intake of gluten in wheat, rye and barley. A strong genetic component has been established for disease with a monozygotic concordance of 75% [16] and 90% of cases possessing the HLA haplotype HLA-DQ2.5 [17] and the remainder mostly have HLA-DQ8 [18]. Despite the role of the HLA, the risk of disease is still greater in HLA matched monozygotic twins compared to HLA matched dizygotic twins [19]. We recently performed a genome wide association and replication study using single nucleotide polymorphisms (SNPs) and identified an additional eight susceptibility loci that predispose to celiac disease [20,21]. A surprising finding from this study was that seven of the eight regions contained promising candidate genes expressed in leucocytes of the immune system. This suggested the feasibility