PubMed:19897031 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/19897031","sourcedb":"PubMed","sourceid":"19897031","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/19897031","text":"An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males.\nThe interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C\u003eT substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (P\u003c0.001) but no repression by the variant allele in any cell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_19897031_1_0","span":{"begin":164,"end":192},"obj":"expanded"},{"id":"SS2_19897031_1_0","span":{"begin":194,"end":197},"obj":"abbr"},{"id":"SS1_19897031_3_0","span":{"begin":543,"end":568},"obj":"expanded"},{"id":"SS2_19897031_3_0","span":{"begin":570,"end":573},"obj":"abbr"},{"id":"SS1_19897031_3_1","span":{"begin":579,"end":599},"obj":"expanded"},{"id":"SS2_19897031_3_1","span":{"begin":601,"end":604},"obj":"abbr"},{"id":"SS1_19897031_4_0","span":{"begin":658,"end":686},"obj":"expanded"},{"id":"SS2_19897031_4_0","span":{"begin":688,"end":691},"obj":"abbr"}],"relations":[{"id":"AE1_19897031_1_0","pred":"abbreviatedTo","subj":"SS1_19897031_1_0","obj":"SS2_19897031_1_0"},{"id":"AE1_19897031_3_0","pred":"abbreviatedTo","subj":"SS1_19897031_3_0","obj":"SS2_19897031_3_0"},{"id":"AE1_19897031_3_1","pred":"abbreviatedTo","subj":"SS1_19897031_3_1","obj":"SS2_19897031_3_1"},{"id":"AE1_19897031_4_0","pred":"abbreviatedTo","subj":"SS1_19897031_4_0","obj":"SS2_19897031_4_0"}],"attributes":[{"subj":"SS1_19897031_1_0","pred":"source","obj":"Allie"},{"subj":"SS2_19897031_1_0","pred":"source","obj":"Allie"},{"subj":"SS1_19897031_3_0","pred":"source","obj":"Allie"},{"subj":"SS2_19897031_3_0","pred":"source","obj":"Allie"},{"subj":"SS1_19897031_3_1","pred":"source","obj":"Allie"},{"subj":"SS2_19897031_3_1","pred":"source","obj":"Allie"},{"subj":"SS1_19897031_4_0","pred":"source","obj":"Allie"},{"subj":"SS2_19897031_4_0","pred":"source","obj":"Allie"}]},{"project":"tmVarCorpus","denotations":[{"id":"T1","span":{"begin":775,"end":785},"obj":"SNP:rs12203592"},{"id":"T2","span":{"begin":896,"end":899},"obj":"DNAMutation:|SUB|C||T"},{"id":"T3","span":{"begin":1039,"end":1049},"obj":"SNP:rs12203592"},{"id":"T4","span":{"begin":1196,"end":1206},"obj":"SNP:rs12203592"}],"attributes":[{"subj":"T1","pred":"source","obj":"tmVarCorpus"},{"subj":"T2","pred":"source","obj":"tmVarCorpus"},{"subj":"T3","pred":"source","obj":"tmVarCorpus"},{"subj":"T4","pred":"source","obj":"tmVarCorpus"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":28,"end":32},"obj":"gene:3662"},{"id":"T1","span":{"begin":111,"end":149},"obj":"disease:C0023452"},{"id":"T2","span":{"begin":458,"end":467},"obj":"gene:5966"},{"id":"T3","span":{"begin":423,"end":435},"obj":"disease:C0006826"},{"id":"T4","span":{"begin":451,"end":456},"obj":"gene:5966"},{"id":"T5","span":{"begin":423,"end":435},"obj":"disease:C0006826"},{"id":"T6","span":{"begin":194,"end":339},"obj":"gene:3662"},{"id":"T7","span":{"begin":423,"end":435},"obj":"disease:C0006826"},{"id":"T8","span":{"begin":486,"end":490},"obj":"gene:3662"},{"id":"T9","span":{"begin":579,"end":604},"obj":"disease:C0024305"},{"id":"T10","span":{"begin":486,"end":490},"obj":"gene:3662"},{"id":"T11","span":{"begin":570,"end":573},"obj":"disease:C0023434"},{"id":"T12","span":{"begin":486,"end":490},"obj":"gene:3662"},{"id":"T13","span":{"begin":543,"end":568},"obj":"disease:C0023434"},{"id":"T14","span":{"begin":622,"end":626},"obj":"gene:3662"},{"id":"T15","span":{"begin":648,"end":686},"obj":"disease:C0023452"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"},{"id":"R8","pred":"associated_with","subj":"T14","obj":"T15"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"},{"subj":"T12","pred":"source","obj":"DisGeNET"},{"subj":"T13","pred":"source","obj":"DisGeNET"},{"subj":"T14","pred":"source","obj":"DisGeNET"},{"subj":"T15","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"19897031-0#28#32#gene3662","span":{"begin":28,"end":32},"obj":"gene3662"},{"id":"19897031-0#111#149#diseaseC0023452","span":{"begin":111,"end":149},"obj":"diseaseC0023452"},{"id":"19897031-3#0#4#gene3662","span":{"begin":486,"end":490},"obj":"gene3662"},{"id":"19897031-3#57#82#diseaseC0023434","span":{"begin":543,"end":568},"obj":"diseaseC0023434"},{"id":"19897031-3#84#87#diseaseC0023434","span":{"begin":570,"end":573},"obj":"diseaseC0023434"},{"id":"19897031-3#93#113#diseaseC0024305","span":{"begin":579,"end":599},"obj":"diseaseC0024305"},{"id":"19897031-3#115#118#diseaseC0024305","span":{"begin":601,"end":604},"obj":"diseaseC0024305"}],"relations":[{"id":"28#32#gene3662111#149#diseaseC0023452","pred":"associated_with","subj":"19897031-0#28#32#gene3662","obj":"19897031-0#111#149#diseaseC0023452"},{"id":"0#4#gene366257#82#diseaseC0023434","pred":"associated_with","subj":"19897031-3#0#4#gene3662","obj":"19897031-3#57#82#diseaseC0023434"},{"id":"0#4#gene366284#87#diseaseC0023434","pred":"associated_with","subj":"19897031-3#0#4#gene3662","obj":"19897031-3#84#87#diseaseC0023434"},{"id":"0#4#gene366293#113#diseaseC0024305","pred":"associated_with","subj":"19897031-3#0#4#gene3662","obj":"19897031-3#93#113#diseaseC0024305"},{"id":"0#4#gene3662115#118#diseaseC0024305","pred":"associated_with","subj":"19897031-3#0#4#gene3662","obj":"19897031-3#115#118#diseaseC0024305"}],"attributes":[{"subj":"19897031-0#28#32#gene3662","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19897031-0#111#149#diseaseC0023452","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19897031-3#0#4#gene3662","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19897031-3#57#82#diseaseC0023434","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19897031-3#84#87#diseaseC0023434","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19897031-3#93#113#diseaseC0024305","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19897031-3#115#118#diseaseC0024305","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"mondo_disease","denotations":[{"id":"T9","span":{"begin":1620,"end":1633},"obj":"Disease"},{"id":"T10","span":{"begin":1630,"end":1633},"obj":"Disease"},{"id":"T1","span":{"begin":111,"end":149},"obj":"Disease"},{"id":"T2","span":{"begin":551,"end":568},"obj":"Disease"},{"id":"T3","span":{"begin":570,"end":573},"obj":"Disease"},{"id":"T5","span":{"begin":579,"end":599},"obj":"Disease"},{"id":"T6","span":{"begin":601,"end":604},"obj":"Disease"},{"id":"T7","span":{"begin":648,"end":686},"obj":"Disease"},{"id":"T8","span":{"begin":688,"end":691},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0000870"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005402"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0001014"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0004948"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0018908"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0018908"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0000870"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0004967"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0000870"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0004967"},{"subj":"T9","pred":"source","obj":"mondo_disease"},{"subj":"T10","pred":"source","obj":"mondo_disease"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"},{"subj":"T3","pred":"source","obj":"mondo_disease"},{"subj":"T5","pred":"source","obj":"mondo_disease"},{"subj":"T6","pred":"source","obj":"mondo_disease"},{"subj":"T7","pred":"source","obj":"mondo_disease"},{"subj":"T8","pred":"source","obj":"mondo_disease"}]},{"project":"PubTator4TogoVar","denotations":[{"id":"39","span":{"begin":775,"end":785},"obj":"SNP"},{"id":"41","span":{"begin":1039,"end":1049},"obj":"SNP"},{"id":"43","span":{"begin":1196,"end":1206},"obj":"SNP"}],"attributes":[{"id":"A39","pred":"resolved_to","subj":"39","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A41","pred":"resolved_to","subj":"41","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A43","pred":"resolved_to","subj":"43","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"subj":"39","pred":"source","obj":"PubTator4TogoVar"},{"subj":"41","pred":"source","obj":"PubTator4TogoVar"},{"subj":"43","pred":"source","obj":"PubTator4TogoVar"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":153,"end":158},"obj":"Body_part"},{"id":"T2","span":{"begin":795,"end":799},"obj":"Body_part"},{"id":"T3","span":{"begin":1339,"end":1344},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000029"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000029"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000029"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"},{"subj":"T2","pred":"source","obj":"Anatomy-MAT"},{"subj":"T3","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":416,"end":422},"obj":"Body_part"},{"id":"T2","span":{"begin":795,"end":808},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000236"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0014403"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":121,"end":149},"obj":"Phenotype"},{"id":"T2","span":{"begin":551,"end":568},"obj":"Phenotype"},{"id":"T3","span":{"begin":579,"end":599},"obj":"Phenotype"},{"id":"T4","span":{"begin":601,"end":604},"obj":"Phenotype"},{"id":"T5","span":{"begin":658,"end":686},"obj":"Phenotype"},{"id":"T6","span":{"begin":688,"end":691},"obj":"Phenotype"},{"id":"T7","span":{"begin":1630,"end":1633},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0006721"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0005526"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0012539"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0012539"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0006721"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"HP:0006721"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"HP:0006721"},{"subj":"T1","pred":"source","obj":"HP-phenotype"},{"subj":"T2","pred":"source","obj":"HP-phenotype"},{"subj":"T3","pred":"source","obj":"HP-phenotype"},{"subj":"T4","pred":"source","obj":"HP-phenotype"},{"subj":"T5","pred":"source","obj":"HP-phenotype"},{"subj":"T6","pred":"source","obj":"HP-phenotype"},{"subj":"T7","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":127,"end":140},"obj":"Cell"},{"id":"T2","span":{"begin":384,"end":391},"obj":"Cell"},{"id":"T3","span":{"begin":416,"end":422},"obj":"Cell"},{"id":"T4","span":{"begin":664,"end":677},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0017005"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000236"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0017005"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T2","pred":"source","obj":"CL-cell"},{"subj":"T3","pred":"source","obj":"CL-cell"},{"subj":"T4","pred":"source","obj":"CL-cell"}]},{"project":"PubTatorOnTogoVar","denotations":[{"id":"39","span":{"begin":775,"end":785},"obj":"SNP"},{"id":"41","span":{"begin":1039,"end":1049},"obj":"SNP"},{"id":"43","span":{"begin":1196,"end":1206},"obj":"SNP"},{"id":"T1","span":{"begin":775,"end":785},"obj":"SNP"},{"id":"T2","span":{"begin":1039,"end":1049},"obj":"SNP"},{"id":"T3","span":{"begin":1196,"end":1206},"obj":"SNP"}],"attributes":[{"id":"A39","pred":"resolved_to","subj":"39","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A41","pred":"resolved_to","subj":"41","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A43","pred":"resolved_to","subj":"43","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A1","pred":"resolved_to","subj":"T1","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A2","pred":"resolved_to","subj":"T2","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"id":"A3","pred":"resolved_to","subj":"T3","obj":"tmVar:rs12203592;VariantGroup:0;CorrespondingGene:3662;RS#:12203592;CorrespondingSpecies:9606"},{"subj":"39","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"41","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"43","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T1","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T2","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T3","pred":"source","obj":"PubTatorOnTogoVar"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#ec939e","default":true},{"id":"tmVarCorpus","color":"#93b8ec"},{"id":"DisGeNET","color":"#d2ec93"},{"id":"DisGeNET5_gene_disease","color":"#ec93ec"},{"id":"mondo_disease","color":"#93ecd2"},{"id":"PubTator4TogoVar","color":"#ecb893"},{"id":"Anatomy-MAT","color":"#9e93ec"},{"id":"Anatomy-UBERON","color":"#a1ec93"},{"id":"HP-phenotype","color":"#ec93bc"},{"id":"CL-cell","color":"#93d6ec"},{"id":"PubTatorOnTogoVar","color":"#ece893"}]}]}}