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dc.contributor.authorKarnes, Jason H
dc.contributor.authorShaffer, Christian M
dc.contributor.authorCronin, Robert
dc.contributor.authorBastarache, Lisa
dc.contributor.authorGaudieri, Silvana
dc.contributor.authorJames, Ian
dc.contributor.authorPavlos, Rebecca
dc.contributor.authorSteiner, Heidi E
dc.contributor.authorMosley, Jonathan D
dc.contributor.authorMallal, Simon
dc.contributor.authorDenny, Joshua C
dc.contributor.authorPhillips, Elizabeth J
dc.contributor.authorRoden, Dan M
dc.date.accessioned2019-04-29T22:47:00Z
dc.date.available2019-04-29T22:47:00Z
dc.date.issued2017-09-01
dc.identifier.citationKarnes, J. H., Shaffer, C. M., Cronin, R. , Bastarache, L. , Gaudieri, S. , James, I. , Pavlos, R. , Steiner, H. E., Mosley, J. D., Mallal, S. , Denny, J. C., Phillips, E. J. and Roden, D. M. (2017), Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin‐Like Receptors (KIR) Types on Heparin‐Induced Thrombocytopenia (HIT). Pharmacotherapy, 37: 1164-1171. doi:10.1002/phar.1983en_US
dc.identifier.issn1875-9114
dc.identifier.pmid28688202
dc.identifier.doi10.1002/phar.1983
dc.identifier.urihttp://hdl.handle.net/10150/632150
dc.description.abstractHeparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10-4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary.en_US
dc.description.sponsorshipVanderbilt CTSA grant from NCATS/NIH [ULTR000445, UL1TR000445]; National Institutes of Health grants from NIGMS/OD [RC2GM092618]; NHGRI/NIGMS [U01HG004603, U19HL065962]; VUMC Clinical Pharmacology Training grant [T32 GM07569]; American Heart Association [16SDG29090005, 15POST22660017]; ACCP Research Institute Futures Grants Award from the American College of Clinical Pharmacyen_US
dc.language.isoenen_US
dc.publisherWILEYen_US
dc.relation.urlhttps://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.1983en_US
dc.rights© 2017 Pharmacotherapy Publications, Inc.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectHLAen_US
dc.subjectelectronic health recordsen_US
dc.subjectheparin-induced thrombocytopeniaen_US
dc.subjectimmunogeneticsen_US
dc.subjectkiller cell immunoglobulin-like receptor (KIR)en_US
dc.subjectpharmacogenomicsen_US
dc.titleInfluence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT)en_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Pharm, Dept Pharm Practice & Scien_US
dc.identifier.journalPHARMACOTHERAPYen_US
dc.description.note12 month embargo; published online: 8 July 2017en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitlePharmacotherapy
refterms.dateFOA2018-07-08T00:00:00Z


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