Tolllike receptor 4 (TLR4) polymorphisms in Tunisian patients with Crohn's disease: genotype-phenotype correlation

<p>Abstract</p> <p>Background</p> <p>The immune responses to bacterial products through the pattern recognition receptor (PRR) play a pivotal role in pathogenesis of Crohn's disease. A recent study described an association between CD and some gene coding for bacterial receptor like NOD2/CARD15 gene and TLR4. In this study, we sought to determine whether TLR4 gene was associated with Crohn's disease (CD) among the Tunisian population and its correlation with clinical manifestation of the disease.</p> <p>Methods</p> <p>90 patients with CD and 80 healthy individuals are genotyped for the <it>Asp299Gly </it>and <it>Thr399Ile </it>polymorphisms by restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>The allele and genotype frequency of the TLR4 polymorphisms did not differ between patients and controls. The genotype-phenotype correlation permitted to show that the <it>Thr399Ile </it>polymorphism was associated with early onset disease.</p> <p>Conclusion</p> <p>this study reported the absence of association between CD and TLR4 gene in the Tunisian population, but this gene could play a role in clinical expression of the disease.</p

Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis

Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP) arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs) and African (21,542 SNPs) populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and associated subpathways can facilitate comprehensive inflammation pathway- focused association analyses

IBD and genetics:New developments

BACKGROUND: Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly understood. Apart from environmental factors, inheritance contributes to IBD. REVIEW: Family studies show an increased risk among family members of a patient with IBD, particularly among first-degree relatives. In twin studies, concordance for disease type and localization is observed. In genetically isolated groups there is a higher prevalence of IBD. For instance. Ashkenazi Jews carry the highest risk. Further evidence comes from animal species that spontaneously develop IBD. Unlike Mendelian inheritance, in complex genetic diseases like IBD, genes are expected to be low penetrant and therefore less prone to selection, which results in higher expected gene frequencies. NOD2/CARD15, the first gene associated with IBD, is a polymorphic gene involved in the innate immune system. The gene has over 60 variations. Three of these play a role in 27% of patients with CD, with a predilection for patients with ileal disease. CONCLUSION: Genetics plays an important role in unravelling the pathogenesis of IBD leading to possible new therapeutic approache

A bleeding disorder caused by a cardiac tumor:case report

A 22-year-old female developed symptomatic thrombocytopenia. On physical examination, apart from ecchymoses. a loud holosystolic murmur was heard. Echocardiography revealed a cardiac rumor. The thrombocytopenia did not respond to corticosteroids, but after surgical removal of the intracardiac tumor, a papillary fibroelastoma, the platelet count normalised. There are no similar case reports in the literature. Our case report illustrates that thrombocytopenia may he associated with a cardiac tumor and that complete physical examination is essential in every patient presenting with easy bruising. (C) 2001 Elsevier Science B.V. All rights reserved