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| |  UEGW: Research Identifies Single Nucleotide Polymorphisms for Crohn's Disease Risk By Chris Berrie PRAGUE, CZECH REPUBLIC -- September 30, 2004 -- Novel genetic associations with Crohn's disease indicate the imminent arrival of a diagnostic genetic panel of single nucleotide polymorphisms (SNPs) for combination with serological and clinical data to identify a patient's risk of the disease, according to a study presented here September 29th at the 12th United European Gastroenterology Week. This study was presented by Dermot McGovern, PhD, Research Fellow, Wellcome Trust Centre for Human Genetics, London, United Kingdom, in collaboration with Professor Derek Jewell, MD, Principal Investigator, Gastroenterology Unit, University of Oxford, Oxford, United Kingdom. One of the benefits of genetic research has been identification of NOD2(CARD15) in the pathogenesis of Crohn's disease, "which has provided a huge insight into the disease pathogenesis and confirmed the heritability in inflammatory bowel disease," Dr. McGovern said. It is now time to turn this advance into providing a more direct benefit for the patient, he added. Based on strong associations with Crohn's disease that have been demonstrated not just for NOD2, but also for IBD5 and TUCAN, the researchers tested a genetic panel of SNPs across patients and healthy controls, with the aim of combining these data in the formation of a "genetic panel" for predicting development of the disease. To perform this fine mapping and candidate gene screening, the researchers applied standard genotyping methods and statistical analyses to 360 robustly phenotyped Crohn's disease patients and 374 healthy controls. One SNP correlation that was found with Crohn's disease related to chromosome 19 and TUCAN; a polymorphism in a cysteine at a stop codon at codon 10 (70.9%; P =.0076; risk ratio, 1.35; 1.08-1.68). Two particular SNPs in other genes of note were also revealed. These are involved in innate immunity, and their significant relevance to the pathogenesis of the disease has been confirmed in a family-based association study, with risk ratios of 1.42 (1.12-1.80; P =.004;) and 1.39 (1.10-1.82; P =.005). These risk genotypes were combined with those of NOD2, IBD5 and TUCAN. Carriage of 3, 4 or 5 of these risk genotypes gave much improved risk ratios: 2.29 (3.66-11.63; P =.0086), 2.85 (2.02-4.03; P < 10-8) and 6.52 (3.66-11.63; P < 10-11), respectively. "However, if we are going to be starting to use genetics clinically, then rather than be talking about relative risk odds ratios, we need to start talking about sensitivity and specificity," Dr. McGovern stressed. He thus recommended a combination of these aspects, as an expression of the likelihood ratios (LRs), which can be positive and negative. Thus, carriage of the 3 NOD2, IBD5 and TUCAN risk genotypes gives a sensitivity of 19.4%, a specificity of 98.0%, and a LR of +9.7. Thus Dr. McGovern said that he was now certain that these recent studies in Crohn's disease genetics would very soon be transferred to the clinic, to the benefit of patients. Furthermore, they are continuing to work on a combination of genetic, serological and clinical data that can be used to devise a clinically relevant CD risk scoring system.
[Presentation title: "From the benchside to the bedside? A genetic panel strongly predicts Crohn's disease. Abstract OP-G-324." Abstract 524]
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