title: Intron 3 of the ARID5B gene: a hot spot for acute lymphoblastic leukemia susceptibility.
abstract: OBJECTIVE
  Single-nucleotide polymorphisms (SNPs) in AT-rich interactive domain 5B (ARID5B) have been associated with risk for pediatric acute lymphoblastic leukemia (ALL). After reviewing previous studies, we realized that the most significant associations were restricted to intron 3, but the mechanism(s) by which those SNPs affect ALL risk remain to be elucidated. Therefore, the aim of this study was to analyze the association between genetic variants of the intron 3 region of ARID5B and the incidence of B-ALL in a Spanish population. We also aimed to find a functional explanation for the association, searching for copy number variations (CNVs), and changes in ARID5B expression associated with the genotypes of the SNPs.
  
  
  METHODS
  We analyzed 10 SNPs in intron 3 of ARID5B in a Spanish population of 219 B-ALL patients and 397 unrelated controls with the Taqman Open Array platform. CNVs were analyzed in 23 patients and 17 controls using the Cytogenetics Whole-genome 2.7 M platform. Expression of ARID5B transcript 1 was quantified by qPCR and related to SNPs genotype in seven ALL cell lines.
  
  
  RESULTS
  Association between intron 3 and B-ALL risk was confirmed for all of the SNPs evaluated in our Spanish population. We could not explain this association by the presence of CNVs. We neither detected changes in the expression of ARID5B isoform associated with the genotype of the SNPs.
  
  
  CONCLUSIONS
  The intron 3 of ARID5B gene was found to be strongly associated with B-ALL risk in the Spanish population examined. However, neither CNVs nor changes in mRNA expression were found to be responsible for this association.
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940, Leioa, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Gutiérrez-Camino
authors.forename: Elixabet
authors.initials: E
authors.lastname: López-López
authors.forename: Idoia
authors.initials: I
authors.lastname: Martín-Guerrero
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Toledo
authors.forename: Nagore
authors.initials: N
authors.lastname: García de Andoin
authors.forename: Ana
authors.initials: A
authors.lastname: Carboné Bañeres
authors.forename: Purificación
authors.initials: P
authors.lastname: García-Miguel
authors.forename: Aurora
authors.initials: A
authors.lastname: Navajas
authors.forename: África
authors.initials: Á
authors.lastname: García-Orad
mesh_terms: D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004171:Diploidy; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors