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dc.contributor.author Lautner-Csorba Orsolya
dc.contributor.author Gézsi András
dc.contributor.author Erdélyi Dániel
dc.contributor.author Hullám Gábor István
dc.contributor.author Antal P
dc.contributor.author Semsei Ágnes F
dc.contributor.author Kutszegi Nóra
dc.contributor.author Kovács Gábor
dc.contributor.author Falus András
dc.contributor.author Szalai Csaba
dc.date.accessioned 2014-12-01T17:28:03Z
dc.date.available 2014-12-01T17:28:03Z
dc.date.issued 2013
dc.identifier 84881114492
dc.identifier.citation pagination=e69843; journalVolume=8; journalIssueNumber=8; journalTitle=PLOS ONE;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/441
dc.identifier.uri doi:10.1371/journal.pone.0069843
dc.description.abstract In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL) or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) methods. Bayesian structure based odds ratios for the relevant variables and interactions were also calculated. Altogether 9 SNPs in 8 genes were associated with altered susceptibility to ALL. After correction for multiple testing, two associations remained significant. The genotype distribution of the MTHFD1 rs1076991 differed significantly between the ALL and control population. Analyzing the subtypes of the disease the GG genotype increased only the risk of B-cell ALL (p = 3.52x10(-4); OR = 2.00). The GG genotype of the rs3776455 SNP in the MTRR gene was associated with a significantly reduced risk to ALL (p = 1.21x10(-3); OR = 0.55), which resulted mainly from the reduced risk to B-cell and hyperdiploid-ALL. The TC genotype of the rs9909104 SNP in the SHMT1 gene was associated with a lower survival rate comparing it to the TT genotype (80.2% vs. 88.8%; p = 0.01). The BN-BMLA confirmed the main findings of the frequentist-based analysis and showed structural interactional maps and the probabilities of the different structural association types of the relevant SNPs especially in the hyperdiploid-ALL, involving additional SNPs in genes like TYMS, DHFR and GGH. We also investigated the statistical interactions and redundancies using structural model properties. These results gave further evidence that polymorphisms in the folate pathway could influence the ALL risk and the effectiveness of the therapy. It was also shown that in gene association studies the BN-BMLA could be a useful supplementary to the traditional frequentist-based statistical method.
dc.relation.ispartof urn:issn:1932-6203
dc.title Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by bayesian relevance and effect size analysis.
dc.type Journal Article
dc.date.updated 2014-11-08T17:42:44Z
dc.language.rfc3066 en
dc.identifier.mtmt 2380146
dc.identifier.wos 000324465000023
dc.identifier.pubmed 23940529
dc.contributor.department SE/ÁOK/K/II. Sz. Gyermekgyógyászati Klinika
dc.contributor.department Budapesti Műszaki és Gazdaságtudományi Egyetem
dc.contributor.department BME/VIK/Méréstechnika és Információs Rendszerek Tanszék
dc.contributor.department SE/ÁOK/I/Genetikai, Sejt- és Immunbiológiai Intézet
dc.contributor.institution Semmelweis Egyetem
dc.contributor.institution Budapesti Műszaki és Gazdaságtudományi Egyetem


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