Sökning: onr:"swepub:oai:DiVA.org:oru-36842" >
Genetic variants in...
-
Wouters, Mira M.Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(författare)
Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome
- Artikel/kapitelEngelska2014
Förlag, utgivningsår, omfång ...
-
2013-09-16
-
BMJ,2014
-
printrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:oru-36842
-
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-36842URI
-
https://doi.org/10.1136/gutjnl-2013-304570DOI
-
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-91263URI
-
https://lup.lub.lu.se/record/4608925URI
-
https://gup.ub.gu.se/publication/189621URI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:129255536URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
Funding Agencies:Fund for Scientific Research (FWO) Flanders, Belgium G.0699.10NFlemish government (Odysseus Program, FWO)Swedish Medical Research Council 13409, 21691, 21692DanoneAstraZeneca
-
Objective: The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS.Design: 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with P-uncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes.Results: Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (P-uncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1.Conclusions: Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Lambrechts, DietherVesalius Research Center, VIB, Leuven University, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, Leuven University, Leuven, Belgium
(författare)
-
Knapp, MichaelInstitute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
(författare)
-
Cleynen, IsabelleTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(författare)
-
Whorwell, PeterDepartment of Medicine, University of Manchester, Manchester, UK
(författare)
-
Agreus, LarsCentre for Family Medicine, Karolinska Institutet, Stockholm, Sweden
(författare)
-
Dlugosz, AldonaKarolinska Institutet
(författare)
-
Schmidt, Peter ThelinKarolinska Institutet
(författare)
-
Halfvarson, Jonas,1970-Örebro universitet,Institutionen för läkarutbildning,Region Örebro län,Department of Internal Medicine(Swepub:oru)jshn
(författare)
-
Simrén, Magnus,1966Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xsimrm
(författare)
-
Ohlsson, BodilLund University,Lunds universitet,Enheten för kroniska inflammatoriska och degenerativa sjukdomar,Forskargrupper vid Lunds universitet,Chronic Inflammatory and Degenerative Diseases Research Unit,Lund University Research Groups(Swepub:lu)kir-boh
(författare)
-
Karling, PontusUmeå universitet,Medicin(Swepub:umu)peakag84
(författare)
-
Van Wanrooy, SanderTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(författare)
-
Mondelaers, StephanieTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(författare)
-
Vermeire, SeverineTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(författare)
-
Lindberg, GregerKarolinska Institutet
(författare)
-
Spiller, RobinQueen's Medical Centre, Nottingham, UK
(författare)
-
Dukes, GeorgeAcademic DPU, GlaxoSmithKline, Research Triangle Park, Durham NC, USA
(författare)
-
D'Amato, MauroKarolinska Institutet
(författare)
-
Boeckxstaens, GuyTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(författare)
-
Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, BelgiumVesalius Research Center, VIB, Leuven University, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, Leuven University, Leuven, Belgium
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Gut: BMJ63:7, s. 1103-11110017-57491468-3288
Internetlänk
Hitta via bibliotek
-
Gut
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- Av författaren/redakt...
-
Wouters, Mira M.
-
Lambrechts, Diet ...
-
Knapp, Michael
-
Cleynen, Isabell ...
-
Whorwell, Peter
-
Agreus, Lars
-
visa fler...
-
Dlugosz, Aldona
-
Schmidt, Peter T ...
-
Halfvarson, Jona ...
-
Simrén, Magnus, ...
-
Ohlsson, Bodil
-
Karling, Pontus
-
Van Wanrooy, San ...
-
Mondelaers, Step ...
-
Vermeire, Severi ...
-
Lindberg, Greger
-
Spiller, Robin
-
Dukes, George
-
D'Amato, Mauro
-
Boeckxstaens, Gu ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Gastroenterologi
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Medicinsk geneti ...
- Artiklar i publikationen
-
Gut
- Av lärosätet
-
Örebro universitet
-
Umeå universitet
-
Lunds universitet
-
Göteborgs universitet
-
Karolinska Institutet