title: Accuracy of SNPs to predict risk of HLA alleles associated with drug-induced hypersensitivity events across racial groups.
abstract: OBJECTIVE
  To evaluate the potential usefulness of selected SNPs to predict specific HLA alleles that are associated with drug-induced hypersensitivity reactions (HSR) in different ethnic groups.
  
  
  RESULTS
  Five specific HLA alleles known to predict HSR were tagged by seven SNPs (rs1061235-HLA-A*31:01; rs2395029-HLA-B*57:01; rs3909184-HLA-B*15:02; rs9469003-HLA-B*58:01; rs3117583-HLA-B*58:01; rs9270986-HLA-DQA1*01:02 and rs3129900-HLA-DQA1*01:02). DNA from 24 African-Americans, 56 Asian, 44 Caucasians and 36 Hispanics of known high resolution HLA-A, B and DQA1 status were genotyped for tagSNPs using TaqMan. Sensitivity and specificity were considered the primary end points and were 100% across the four populations for rs2395029-HLA-B*57:01. SNP prediction of HLA-A*31:01 had 100% sensitivity and 84% specificity.
  
  
  CONCLUSIONS
  This study demonstrates the utility of SNP tagging as a 'real time' approach to predict or exclude the presence of specific HLA alleles of known importance to HSR across diverse ethnic groups. Original submitted 24 April 2014; Revision submitted 2 April 2015.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, PR China.|UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.|Pharmacogenetics for Every Nation Initiative, Chapel Hill, NC, USA.|Moffitt Cancer Center, DeBartolo Family Personalized Medicine Institute, Tampa, FL, USA.
authors.forename: Yijing
authors.initials: Y
authors.lastname: He
authors.affiliation: Gentris Corporation, 133 Southcenter Ct, Morrisville, NC 27560, USA.
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Hoskins
authors.affiliation: Gentris Corporation, 133 Southcenter Ct, Morrisville, NC 27560, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Clark
authors.affiliation: Gentris Corporation, 133 Southcenter Ct, Morrisville, NC 27560, USA.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Campbell
authors.affiliation: Gentris Corporation, 133 Southcenter Ct, Morrisville, NC 27560, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Wagner
authors.affiliation: UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.|Pharmacogenetics for Every Nation Initiative, Chapel Hill, NC, USA.|Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Motsinger-Reif
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, PR China.|UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.|Pharmacogenetics for Every Nation Initiative, Chapel Hill, NC, USA.|Moffitt Cancer Center, DeBartolo Family Personalized Medicine Institute, Tampa, FL, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D044466:Asian People / Q000235:genetics; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People
chemical_list: D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen
keywords: HLA; drug-induced hypersensitivity; human leukocyte antigen; pharmacogenetics; pharmacogenomics; risk mitigation