{"corpus_id":11671167,"paper_sha":"36210154fd76e672a5796b1485be828c3aadfe98","doi":"10.1056/NEJMOA021986","arxiv_id":null,"pmid":12686700,"pmcid":null,"mag_id":2063288921,"dblp_id":null,"acl_id":null,"title":"Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1.","year":2003,"publication_date":"2003-04-10","venue":"New England Journal of Medicine","journal":{"name":"The New England journal of medicine","pages":"\n          1442-8\n        ","volume":"348 15"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine"],"reference_count":33,"citation_count":679,"influential_citation_count":35,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"ATP Binding Cassette Transporter, Subfamily B, Member 1","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D020168"},{"d":"Case-Control Studies","mj":false,"ui":"D016022"},{"d":"Drug Resistance, Multiple","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D018432"},{"d":"Epilepsy","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D004827"},{"d":"Gene Frequency","mj":false,"ui":"D005787"},{"d":"Genes, MDR","mj":true,"ui":"D019450"},{"d":"Genotype","mj":false,"ui":"D005838"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Linkage Disequilibrium","mj":false,"ui":"D015810"},{"d":"Polymorphism, Genetic","mj":true,"ui":"D011110"}],"chemicals":[{"n":"ATP Binding Cassette Transporter, Subfamily B, Member 1","ui":"D020168","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nejm.org/doi/pdf/10.1056/NEJMoa021986?articleTools=true","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/36210154fd76e672a5796b1485be828c3aadfe98","s2_open_access_license":null,"s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"BACKGROUND\nOne third of patients with epilepsy have drug-resistant epilepsy, which is associated with an increased risk of death and debilitating psychosocial consequences. Because this form is resistant to multiple antiepileptic drugs, the mode of resistance must be nonspecific, involving drug-efflux transporters such as ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 and P-glycoprotein 170). We hypothesized that the CC genotype at the ABCB1 C3435T polymorphism, which is associated with increased expression of the protein, influences the response to antiepileptic-drug treatment.\n\n\nMETHODS\nABCB1 3435 was genotyped in 315 patients with epilepsy, classified as drug-resistant in 200 and drug-responsive in 115, and 200 control subjects without epilepsy. Recently devised methods were used to control for population stratification, and linkage disequilibrium was calculated across the gene.\n\n\nRESULTS\nAs compared with patients with drug-responsive epilepsy, patients with drug-resistant epilepsy were more likely to have the CC genotype at ABCB1 3435 than the TT genotype (odds ratio, 2.66; 95 percent confidence interval, 1.32 to 5.38; P=0.006). There was no genetic stratification between the two groups of patients. The polymorphism fell within an extensive block of linkage disequilibrium spanning much or all of the gene, implying that the polymorphism may not itself be causal but rather may be linked with the causal variant.\n\n\nCONCLUSIONS\nThese pharmacogenomic results identify a genetic factor associated with resistance to antiepileptic drugs.","claims":[{"public_id":"cl_64cc7f9e3a60c207e4ffd3126ff57b29","status":"active","text":"ABCB1 is identified as a genetic factor associated with resistance to antiepileptic drugs.","confidence":0.88,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_64cc7f9e3a60c207e4ffd3126ff57b29"},{"public_id":"cl_6fd48c0aeb1a46f86f1d205c1327e9fc","status":"active","text":"Patients with drug-resistant epilepsy were more likely to have the CC genotype at ABCB1 3435 than the TT genotype, with an odds ratio of 2.66 and a 95% confidence interval of 1.32 to 5.38.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_6fd48c0aeb1a46f86f1d205c1327e9fc"},{"public_id":"cl_8c14e470d6dd7ef711f8c57de181eea0","status":"active","text":"The ABCB1 C3435T CC genotype is associated with drug-resistant epilepsy compared with drug-responsive epilepsy.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_8c14e470d6dd7ef711f8c57de181eea0"},{"public_id":"cl_35e5b60c17dc4793d88fec24f413e752","status":"active","text":"The polymorphism lies within a large linkage disequilibrium block spanning much or all of ABCB1, suggesting it may be linked to the causal variant rather than being causal itself.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_35e5b60c17dc4793d88fec24f413e752"}],"concepts":[{"public_id":"co_0228e00d0c2af80b19da6e6a94370e26","status":"active","name":"CC genotype","description":"The homozygous genotype carrying two cytosine alleles at the polymorphic site.","types":["genotype"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0228e00d0c2af80b19da6e6a94370e26"},{"public_id":"co_218d3375b53b83c5a00afbba0c9da505","status":"active","name":"ABCB1 C3435T polymorphism","description":"A genetic variation in ABCB1 at nucleotide position 3435 involving a C-to-T substitution.","types":["genetic variant"],"aliases":["C3435T polymorphism"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_218d3375b53b83c5a00afbba0c9da505"},{"public_id":"co_2c5f1b3384f43008e391be03588185fd","status":"active","name":"ABCB1","description":"A drug-transporter gene that encodes P-glycoprotein 170 and is also known as MDR1.","types":["gene"],"aliases":["MDR1","P-glycoprotein 170"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2c5f1b3384f43008e391be03588185fd"},{"public_id":"co_6a254e4b17fc7e8164002a4173f047f8","status":"active","name":"drug-responsive epilepsy","description":"Epilepsy that responds to antiepileptic drug treatment.","types":["condition"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_6a254e4b17fc7e8164002a4173f047f8"},{"public_id":"co_7e29eab9156117ff662bd3c3a31eba0f","status":"active","name":"causal variant","description":"A genetic variant that directly contributes to a biological trait or phenotype.","types":["genetic variant"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7e29eab9156117ff662bd3c3a31eba0f"},{"public_id":"co_a2d14d7850e9d2e22bc5185dbdabcd44","status":"active","name":"linkage disequilibrium block","description":"A genomic region in which variants are inherited together more often than expected by chance.","types":["genomic 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