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Genetic variants in...
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Wouters, Mira M.Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
(author)
Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2013-09-16
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BMJ,2014
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:oru-36842
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-36842URI
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https://doi.org/10.1136/gutjnl-2013-304570DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-91263URI
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https://lup.lub.lu.se/record/4608925URI
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https://gup.ub.gu.se/publication/189621URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:129255536URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies:Fund for Scientific Research (FWO) Flanders, Belgium G.0699.10NFlemish government (Odysseus Program, FWO)Swedish Medical Research Council 13409, 21691, 21692DanoneAstraZeneca
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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.
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Lambrechts, DietherVesalius Research Center, VIB, Leuven University, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, Leuven University, Leuven, Belgium
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Knapp, MichaelInstitute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
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Cleynen, IsabelleTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
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Whorwell, PeterDepartment of Medicine, University of Manchester, Manchester, UK
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Agreus, LarsCentre for Family Medicine, Karolinska Institutet, Stockholm, Sweden
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Dlugosz, AldonaKarolinska Institutet
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Schmidt, Peter ThelinKarolinska Institutet
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Halfvarson, Jonas,1970-Örebro universitet,Institutionen för läkarutbildning,Region Örebro län,Department of Internal Medicine(Swepub:oru)jshn
(author)
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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
(author)
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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
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Karling, PontusUmeå universitet,Medicin(Swepub:umu)peakag84
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Van Wanrooy, SanderTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
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Mondelaers, StephanieTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
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Vermeire, SeverineTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
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Lindberg, GregerKarolinska Institutet
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Spiller, RobinQueen's Medical Centre, Nottingham, UK
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Dukes, GeorgeAcademic DPU, GlaxoSmithKline, Research Triangle Park, Durham NC, USA
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D'Amato, MauroKarolinska Institutet
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Boeckxstaens, GuyTranslational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
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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)
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In:Gut: BMJ63:7, s. 1103-11110017-57491468-3288
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Wouters, Mira M.
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Lambrechts, Diet ...
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Knapp, Michael
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Cleynen, Isabell ...
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Whorwell, Peter
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Agreus, Lars
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Dlugosz, Aldona
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Ohlsson, Bodil
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Karling, Pontus
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Vermeire, Severi ...
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Lindberg, Greger
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