TITLE

CARD15 and HLA DRB1 Alleles Influence Susceptibility and Disease Localization in Crohn's Disease

AUTHOR(S)
Newman, Bill; Silverberg, Mark S.; Xiangjun Gu; Qing Zhang; Lazaro, Ana; Steinhart, A. Hillary; Greenberg, Gordon R.; Griffiths, Anne M.; McLeod, Robin S.; Cohen, Zane; Fernández-Viña, Marcelo; Amos, Christopher I.; Siminovitch, Katherine
PUB. DATE
February 2004
SOURCE
American Journal of Gastroenterology;Feb2004, Vol. 99 Issue 2, p306
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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).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.
ACCESSION #
14816747

 

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