Background: Genome-wide association studies (GWAS) in Crohn’s disease (CD) have identified associations with single-nucleotide polymorphism (SNP) rs11175593 at chromosome 12q12. The MUC19 and LRRK2 genes reside close to the GWAS signal, but it is as yet unclear which of the 2 genes represent the CD susceptibility genes.
Methods: We studied associations between nonsynonymous coding variants in the MUC19 (5) and LRRK2 (3) genes in a case–control sample comprising CD cases aged <18 years at diagnosis. The GWAS lead SNP rs11175593 was also investigated. Allelic, genotype, and haplotype associations were examined assuming different models of inheritance.
Results: A total of 530 cases and 600 controls were studied. The mean (±SD) age at diagnosis was 12.4 (±3.3). Most cases were male (57.4%). Most patients had ileocolonic disease location (48.8%) and inflammatory behavior at diagnosis (87.0%). Three MUC19 SNPs were nominally significantly associated with CD (rs11564245, Asp→His: P = 0.02; rs4768261, Ser→Phe: P = 0.0008; and rs2933353, Glu→Ala: P = 0.01). Associations with rs4768261 were maintained after corrections for multiple comparisons (permuted, P = 0.007). None of the LRRK2 SNPs were associated with CD. Haplotype analysis supported the single SNP associations noted with the MUC19 gene.
Conclusions: GWAS signal at chromosome 12q12 for CD may represent associations with the MUC19 gene.
Article first published online 9 April 2013
*Division of Gastroenterology, Hepatology & Nutrition, Research Centre, CHU-Ste-Justine, Montreal, Canada;
†Division of Gastroenterology, Children’s Hospital of Eastern Ontario, Ottawa, Canada;
‡Department of Gastroenterology, Research Institute, McGill University, Montreal, Quebec, Canada;
§Division of Gastroenterology, Hepatology & Nutrition, British Columbia’s Children’s Hospital, Vancouver, Canada;
‖Department of Preventive and Social Medicine, University of Montreal, Montreal, Canada;
¶Center for Communicable Diseases and Infection Control, Public Health Agency of Canada, Montreal, Canada;
**Division of Orthopaedics, Department of Paediatrics, University of Montreal, Montreal, Canada;
††Division of Gastroenterology, Faculty of Medicine, the Research Institute of the McGill University Health Center, McGill University, Montreal, Canada; and
‡‡Department of Nutrition, University of Montreal, Montreal, Canada.
Reprints: Devendra K. Amre, MBBS, PhD, Research Center, CHU-Ste-Justine, Bureau 3734, Ste-Justine Hospital, 3175 Cote-Sainte-Catherine, Montreal, Quebec, Canada H3T 1C5 (e-mail: email@example.com).
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Supported by the Canadian Institutes of Health Research (CIHR-IBD NET GRANT, Institute of Infection & Immunity).
D. K. Amre was supported by a research salary award from the Fonds de la Recherché en Santé du Québec (FRSQ), Quebec, Canada. I. Costea was supported by a doctoral award from the FRSQ. A. Krupoves was supported by a scholarship from the Sainte-Justine Hospital Foundation, Montreal, Canada, and by a scholarship from the PhD Program of the University of Montreal, Montreal, Canada.
Received October 16, 2012
Accepted November 13, 2012