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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is a chronic inflammatory disease of the gut associated with allelic variants of CARD15 and HLA-DRB1 genes. We investigated the prevalence and effects of these variants in a Canadian CD cohort. METHODS: 507 unrelated CD patients were genotyped for the three major CD-associated variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) and for thirteen HLA-DRB1 alleles. RESULTS: At least one CARD15 variant was present in 32.5% of the CD patients compared with 20% of controls. The prevalence of CARD15 mutation was similar in both sporadic and familial and Jewish and non-Jewish CD patients. The Gly908Arg variant was significantly higher and the Arg702Trp variant significantly lower in Jewish compared to non-Jewish patients. A positive association between the HLA-DRB1*0103 allele and CD was detected in non-Jewish, familial cases (p = 0.0002), with risk for CD increased by 6.7 fold by the presence of an HLA-DRB1*0103 allele as compared to 1.9 fold and 19 fold by a single or two CARD15 variant alleles, respectively. We show a significant association of ileal involvement with CARD15 variants (OR = 1.8; p = 0.02), HLA-DRB1*0701 (OR = 1.9; p = 0.006) and DRB1*04 (OR = 1.7; p = 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients. By contrast, the HLA-DRB1*0103 allele was associated with later age of diagnosis (p = 0.02) and pure colonic disease (p = 0.000013). CONCLUSIONS: These observations confirm the influence of CARD15 and HLA-DRB1 alleles on both CD susceptibility and site of disease and identify genotyping of these variants as a potential tool for improved diagnosis and risk prediction in CD.[1]


  1. CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease. Newman, B., Silverberg, M.S., Gu, X., Zhang, Q., Lazaro, A., Steinhart, A.H., Greenberg, G.R., Griffiths, A.M., McLeod, R.S., Cohen, Z., Fernández-Viña, M., Amos, C.I., Siminovitch, K. Am. J. Gastroenterol. (2004) [Pubmed]
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