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dc.contributor.authorBartram, T
dc.contributor.authorSchütte, P
dc.contributor.authorMöricke, A
dc.contributor.authorHoulston, RS
dc.contributor.authorEllinghaus, E
dc.contributor.authorZimmermann, M
dc.contributor.authorBergmann, A
dc.contributor.authorLöscher, B-S
dc.contributor.authorKlein, N
dc.contributor.authorHinze, L
dc.contributor.authorJunk, SV
dc.contributor.authorForster, M
dc.contributor.authorBartram, CR
dc.contributor.authorKöhler, R
dc.contributor.authorFranke, A
dc.contributor.authorSchrappe, M
dc.contributor.authorKratz, CP
dc.contributor.authorCario, G
dc.contributor.authorStanulla, M
dc.date.accessioned2022-01-07T14:24:24Z
dc.date.available2022-01-07T14:24:24Z
dc.date.issued2021-10-20
dc.identifier.citationJournal of clinical medicine, 2021, 10 (21)
dc.identifier.issn2077-0383
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4953
dc.identifier.eissn2077-0383
dc.identifier.doi10.3390/jcm10214815
dc.description.abstractBackground Acute pancreatitis (AP) is a serious, mechanistically not entirely resolved side effect of L-asparaginase-containing treatment for acute lymphoblastic leukemia (ALL). To find new candidate variations for AP, we conducted a genome-wide association study (GWAS). Methods In all, 1,004,623 single-nucleotide variants (SNVs) were analyzed in 51 pediatric ALL patients with AP (cases) and 1388 patients without AP (controls). Replication used independent patients. Results The top-ranked SNV (rs4148513) was located within the ABCC4 gene (odds ratio (OR) 84.1; p = 1.04 × 10 -14 ). Independent replication of our 20 top SNVs was not supportive of initial results, partly because rare variants were neither present in cases nor present in controls. However, results of combined analysis (GWAS and replication cohorts) remained significant (e.g., rs4148513; OR = 47.2; p = 7.31 × 10 -9 ). Subsequently, we sequenced the entire ABCC4 gene and its close relative, the cystic fibrosis associated CFTR gene, a strong AP candidate gene, in 48 cases and 47 controls. Six AP-associated variants in ABCC4 and one variant in CFTR were detected. Replication confirmed the six ABCC4 variants but not the CFTR variant. Conclusions Genetic variation within the ABCC4 gene was associated with AP during the treatment of ALL. No association of AP with CFTR was observed. Larger international studies are necessary to more conclusively assess the risk of rare clinical phenotypes.
dc.formatElectronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGenetic Variation in <i>ABCC4</i> and <i>CFTR</i> and Acute Pancreatitis during Treatment of Pediatric Acute Lymphoblastic Leukemia.
dc.typeJournal Article
dcterms.dateAccepted2021-10-18
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/jcm10214815
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-10-20
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of clinical medicine
pubs.issue21
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.publication-statusPublished
pubs.volume10
pubs.embargo.termsNot known
icr.researchteamCancer Genomics
dc.contributor.icrauthorHoulston, Richarden_US


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