Evidence of interaction of card8 rs2043211 with nalp3 rs35829419 in crohn's disease

ABSTRACT The location of CARD8 within an inflammatory bowel disease (IBD) locus and its role in the NALP3 inflammasome and as a nuclear factor (NF)_κ_B inhibitor make it an attractive

candidate risk gene for IBD. However, studies testing for the association of the _CARD8_ loss-of-function single-nucleotide polymorphism (SNP) _rs2043211_ with IBD have yielded mixed

results. A recent study provided evidence that this discordance may result from an interaction of _rs2043211_ with loss-of-function variants in nucleotide-binding oligomerization domain

protein 2 (_NOD2)_ and a gain-of-function SNP (_rs35829419_) in _NALP3_. To confirm this interaction, we conducted a replication in an independent IBD sample set (_n_=1009 patients, _n_=517

controls). We found that the presence of the minor allele of _rs2043211_ with the major allele of _rs35829419_ conferred a protective effect against Crohn's disease (and vice versa),

which intensified in the absence of _NOD2_ mutations (_P_1,2/1,1=0.009, odds ratio (OR)=0.66, 95% confidence interval (CI) (0.48–0.90); _P_1,1/1,2=0.015, OR=0.35, 95% CI (0.15–0.82)). We

propose that these genotype combinations protect against gut inflammation by preventing the NALP3 inflammasome from producing excessive interleukin-1_β_. Access through your institution Buy

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blood. _Anal Biochem_ (1988); 174: 485–488. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the people of Canterbury with IBD who generously gave of their time to

take part in the study. We also thank Rhondda Brown and Judy Hoar for their assistance in coordinating the recruitment of patients to the Canterbury IBD sample set, and Pip Shirley, Megan

Reilly, David Tan, Ramez Ailabouni and Charlotte Duncan for entering patient details into the clinical database. This study was supported by the Health Research Council (HRC) of New Zealand,

the New Zealand Lottery Health Board and the University of Otago. RLR is the recipient of a Sir Charles Hercus Health Research Fellowship (HRC). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Department of Biochemistry, University of Otago, Dunedin, New Zealand R L Roberts, R K G Topless, A J Phipps-Green & T R Merriman * Department of Medicine, University of Otago,

Christchurch, New Zealand R L Roberts, R B Gearry & M L Barclay * Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand R B Gearry & M L Barclay Authors *

R L Roberts View author publications You can also search for this author inPubMed Google Scholar * R K G Topless View author publications You can also search for this author inPubMed Google

Scholar * A J Phipps-Green View author publications You can also search for this author inPubMed Google Scholar * R B Gearry View author publications You can also search for this author

inPubMed Google Scholar * M L Barclay View author publications You can also search for this author inPubMed Google Scholar * T R Merriman View author publications You can also search for

this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to R L Roberts. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Roberts, R., Topless, R., Phipps-Green, A. _et al._ Evidence of interaction of _CARD8 rs2043211_ with _NALP3

rs35829419_ in Crohn's disease. _Genes Immun_ 11, 351–356 (2010). https://doi.org/10.1038/gene.2010.11 Download citation * Received: 11 November 2009 * Revised: 11 January 2010 *

Accepted: 29 January 2010 * Published: 25 February 2010 * Issue Date: June 2010 * DOI: https://doi.org/10.1038/gene.2010.11 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * inflammasome * _TUCAN_ * inflammatory bowel disease * ulcerative colitis * _NOD2_ * _CARD15_