NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2

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dc.contributor.authorMuise, Aleixo M.
dc.contributor.authorXu, Wei
dc.contributor.authorGuo, Cong Hui
dc.contributor.authorWalters, Thomas D.
dc.contributor.authorWolters, Victorien M.
dc.contributor.authorFattouh, Ramzi
dc.contributor.authorLam, Grace Y.
dc.contributor.authorHu, Pingzhao
dc.contributor.authorMurchie, Ryan
dc.contributor.authorSherlock, Mary
dc.contributor.authorCristobal Gana, Juan
dc.contributor.authorRussell, Richard K.
dc.contributor.authorGlogauer, Michael
dc.contributor.authorDuerr, Richard H.
dc.contributor.authorCho, Judy H.
dc.contributor.authorLees, Charlie W.
dc.contributor.authorSatsangi, Jack
dc.contributor.authorWilson, David C.
dc.contributor.authorPaterson, Andrew D.
dc.contributor.authorGriffiths, Anne M.
dc.contributor.authorSilverberg, Mark S.
dc.contributor.authorBrumell, John H.
dc.contributor.authorNEOPICS
dc.date.accessioned2024-01-10T13:15:20Z
dc.date.available2024-01-10T13:15:20Z
dc.date.issued2012
dc.description.abstractObjective The NOX2 NADPH oxidase complex produces reactive oxygen species and plays a critical role in the killing of microbes by phagocytes. Genetic mutations in genes encoding components of the complex result in both X-linked and autosomal recessive forms of chronic granulomatous disease (CGD). Patients with CGD often develop intestinal inflammation that is histologically similar to Crohn's colitis, suggesting a common aetiology for both diseases. The aim of this study is to determine if polymorphisms in NOX2 NADPH oxidase complex genes that do not cause CGD are associated with the development of inflammatory bowel disease (IBD).
dc.description.abstractMethods Direct sequencing and candidate gene approaches were used to identify susceptibility loci in NADPH oxidase complex genes. Functional studies were carried out on identified variants. Novel findings were replicated in independent cohorts.
dc.description.abstractResults Sequence analysis identified a novel missense variant in the neutrophil cytosolic factor 2 (NCF2) gene that is associated with very early onset IBD (VEO-IBD) and subsequently found in 4% of patients with VEO-IBD compared with 0.2% of controls (p=1.3x10(-5), OR 23.8 (95% CI 3.9 to 142.5); Fisher exact test). This variant reduced binding of the NCF2 gene product p67(phox) to RAC2. This study found a novel genetic association of RAC2 with Crohn's disease (CD) and replicated the previously reported association of NCF4 with ileal CD.
dc.description.abstractConclusion These studies suggest that the rare novel p67(phox) variant results in partial inhibition of oxidase function and are associated with CD in a subgroup of patients with VEO-IBD; and suggest that components of the NADPH oxidase complex are associated with CD.
dc.description.funderCrohn's and Colitis Foundation of Canada (CCFC)/Canadian Association of Gastroenterology (CAG)/Canadian Institute for Health Research (CIHR)
dc.description.funderCIHR
dc.description.funderOntario Ministry of Research and Innovation
dc.description.funderCDHNF/NASPGHAN
dc.description.funderMedical Research Council Patient Cohorts Research Initiative
dc.description.funderWellcome Trust
dc.description.funderChief Scientist Office of the Scottish Government Health Department
dc.description.funderUniversity of Edinburgh
dc.description.funderNIH/NIDDK
dc.description.funderGale and Graham Wright Research Chair in Digestive Diseases at Mount Sinai Hospital
dc.description.funderCCFC
dc.description.funderBurroughs Wellcome Fund
dc.description.funderNATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
dc.description.funderMedical Research Council
dc.description.funderChief Scientist Office
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent8 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1136/gutjnl-2011-300078
dc.identifier.eissn1468-3288
dc.identifier.issn0017-5749
dc.identifier.pubmedidMEDLINE:21900546
dc.identifier.urihttps://doi.org/10.1136/gutjnl-2011-300078
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78492
dc.identifier.wosidWOS:000304443200012
dc.information.autorucMedicina;Gana J;S/I;8726
dc.issue.numero7
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1035
dc.pagina.inicio1028
dc.publisherBMJ PUBLISHING GROUP
dc.revistaGUT
dc.rightsacceso restringido
dc.subjectINFLAMMATORY-BOWEL-DISEASE
dc.subjectGENOME-WIDE ASSOCIATION
dc.subjectCROHNS-DISEASE
dc.subjectNEUTROPHIL DYSFUNCTION
dc.subjectSUSCEPTIBILITY
dc.subjectACTIVATION
dc.subjectCOLITIS
dc.subjectLOCI
dc.subjectAUTOPHAGY
dc.subjectMUTATION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2
dc.typeartículo
dc.volumen61
sipa.codpersvinculados8726
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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