ABSTRACT
Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10(GGGG)) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio=1.89, P-value=0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10(GGGG) haplotype (P(c)<0.0001). The interaction gain attributed to the combination of both genes was negative (IG=-2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes.
Subject(s)
Crohn Disease/genetics , Genetic Predisposition to Disease , Nod2 Signaling Adaptor Protein/genetics , Toll-Like Receptor 10/genetics , Adolescent , Adult , Alleles , Case-Control Studies , Child , Female , Gene Frequency , Haplotypes , Humans , Male , Middle Aged , Models, Genetic , Phenotype , Polymorphism, Single Nucleotide , Toll-Like Receptor 1/genetics , Toll-Like Receptor 6/genetics , Young AdultABSTRACT
Sulphasalazine is the drug most widely used in intestinal inflammatory disease given its efficacy and low cost. Nonetheless, its administration is not lacking adverse effects. Two cases of severe hypersensitivity are herein described. Moreover, the diagnostic difficulties observed and their implication in the management of the underlying disease are discussed.