GOALS: To establish the relevance of variants in the IL-23R and ATG16L1 genes in inflammatory bowel disease (IBD). AIM: Three recent genome wide association studies have identified variants in the IL-23R and ATG16L1 genes, which modulate susceptibility to Crohn's disease (CD). METHODS: We genotyped 1028 IBD patients, including 443 CD and 347 ulcerative colitis (UC) non-Jewish cases, 238 (183 CD and 55 UC) Jewish cases, and 1005 ethnically matched control subjects for 18 and 11 variants, respectively, in the IL-23R and ATG16L1 genes, including the IL-23R (R381Q) and ATG16L1 (T216A) variants, previously associated with CD. RESULTS: Single nucleotide polymorphisms within each of 3 haplotype blocks across the IL-23R gene were associated with an increased risk of CD. Notably, the minor allele of the IL-23R R381Q variant was present in 2.9% of cases and 6.0% controls (P=0.0001, odds ratio=0.48, 95% confidence interval 0.33-0.69). Homozygosity for the minor (T) allele of the ATG16L1 T216A polymorphism was strongly protective for CD (P=0.0001, odds ratio=0.51, 95% confidence interval 0.38-0.68). No phenotypic associations were detected and no interactions between the genes to increase disease risk were established. CONCLUSIONS: We confirm the association of CD with variants in the IL-23R and ATG16L1 genes and the more modest association of the IL-23R R381Q variant with UC. Our results also suggest that these variants act independently of one another to influence risk and pathogenesis of IBD.
GOALS: To establish the relevance of variants in the IL-23R and ATG16L1 genes in inflammatory bowel disease (IBD). AIM: Three recent genome wide association studies have identified variants in the IL-23R and ATG16L1 genes, which modulate susceptibility to Crohn's disease (CD). METHODS: We genotyped 1028 IBD patients, including 443 CD and 347 ulcerative colitis (UC) non-Jewish cases, 238 (183 CD and 55 UC) Jewish cases, and 1005 ethnically matched control subjects for 18 and 11 variants, respectively, in the IL-23R and ATG16L1 genes, including the IL-23R (R381Q) and ATG16L1 (T216A) variants, previously associated with CD. RESULTS: Single nucleotide polymorphisms within each of 3 haplotype blocks across the IL-23R gene were associated with an increased risk of CD. Notably, the minor allele of the IL-23RR381Q variant was present in 2.9% of cases and 6.0% controls (P=0.0001, odds ratio=0.48, 95% confidence interval 0.33-0.69). Homozygosity for the minor (T) allele of the ATG16L1T216A polymorphism was strongly protective for CD (P=0.0001, odds ratio=0.51, 95% confidence interval 0.38-0.68). No phenotypic associations were detected and no interactions between the genes to increase disease risk were established. CONCLUSIONS: We confirm the association of CD with variants in the IL-23R and ATG16L1 genes and the more modest association of the IL-23RR381Q variant with UC. Our results also suggest that these variants act independently of one another to influence risk and pathogenesis of IBD.
Authors: Matti Waterman; Wei Xu; Joanne M Stempak; Raquel Milgrom; Charles N Bernstein; Anne M Griffiths; Gordon R Greenberg; A Hillary Steinhart; Mark S Silverberg Journal: Inflamm Bowel Dis Date: 2010-12-10 Impact factor: 5.325
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Authors: Inga Peter; Adele A Mitchell; Laurie Ozelius; Monica Erazo; Jianzhong Hu; Dana Doheny; Maria T Abreu; Daniel H Present; Thomas Ullman; Keith Benkov; Burton I Korelitz; Lloyd Mayer; Robert J Desnick Journal: BMC Med Genet Date: 2011-05-06 Impact factor: 2.103