Brief Article
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World J Gastroenterol. Jun 21, 2011; 17(23): 2829-2837
Published online Jun 21, 2011. doi: 10.3748/wjg.v17.i23.2829
NOD2 and ATG16L1 polymorphisms affect monocyte responses in Crohn’s disease
Dylan M Glubb, Richard B Gearry, Murray L Barclay, Rebecca L Roberts, John Pearson, Jacqui I Keenan, Judy McKenzie, Robert W Bentley
Dylan M Glubb, Department of Medicine, University of Chicago, IL 60637-1470, United States
Richard B Gearry, Murray L Barclay, Rebecca L Roberts, Department of Medicine, University of Otago, Christchurch, 8140, New Zealand
Richard B Gearry, Murray L Barclay, Department of Gastroenterology, Christchurch Hospital, Christchurch, 8140, New Zealand
Rebecca L Roberts, Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand
John Pearson, Department of Pathology, University of Otago, Christchurch, 8140, New Zealand
Jacqui I Keenan, Department of Surgery, University of Otago, Christchurch, 8140, New Zealand
Judy McKenzie, Department of Haematology, University of Otago, Christchurch, 8140, New Zealand
Robert W Bentley, Department of Paediatrics, University of Otago, Christchurch, 8140, New Zealand
Author contributions: Glubb DM, McKenzie J and Bentley RW performed the research; Glubb DM, Roberts RL, Bentley RW and Gearry RB designed the research; Pearson J, Glubb DM, Roberts RL and Bentley RW analyzed the data; Barclay ML and Gearry RB provided patient samples; all authors contributed to the writing of the manuscript.
Supported by Broad Medical Research Program of The Broad Foundation, Inflammatory Bowel Disease Grant IBD-0236. RLR is the recipient of a Sir Charles Hercus Health Research Fellowship from the Health Research Council of New Zealand
Correspondence to: Robert W Bentley, PhD, Department of Paediatrics, University of Otago, PO Box 4345, Christchurch 8140, New Zealand. robert.bentley@otago.ac.nz
Telephone: +64-3-3641558 Fax: +64-3-3640009
Received: July 1, 2010
Revised: September 30, 2010
Accepted: October 7, 2010
Published online: June 21, 2011
Abstract

AIM: To assess whether polymorphisms in NOD2 and ATG16L1 affect cytokine responses and mycobacterium avium subspecies paratuberculosis (MAP) survival in monocytes from Crohn’s disease (CD) patients.

METHODS: Monocytes were isolated from peripheral blood of CD patients of known genotype for common single nucleotide polymorphisms of NOD2 and ATG16L1. Monocytes were challenged with MAP and bacterial persistence assessed at subsequent time-points. Cytokine responses were assayed using a Milliplex multi-analyte profiling assay for 13 cytokines.

RESULTS: Monocytes heterozygous for a NOD2 polymorphism (R702W, P268S, or 1007fs) were more permissive for growth of MAP (P = 0.045) than those without. There was no effect of NOD2 genotype on subsequent cytokine expression. The T300A polymorphism of ATG16L1 did not affect growth of MAP in our model (P = 0.175), but did increase expression of cytokines interleukin (IL)-10 (P = 0.047) and IL-6 (P = 0.019).

CONCLUSION: CD-associated polymorphisms affected the elimination of MAP from ex vivo monocytes (NOD2), or expression of certain cytokines (ATG16L1), implying independent but contributory roles in the pathogenesis of CD.

Keywords: Inflammatory bowel disease, Mycobacterium avium subspecies paratuberculosis, Cytokine, CARD15, Autophagy