Yijing He1,2,3,4, Janelle M Hoskins5, Scott Clark5, Nathan H Campbell5, Kim Wagner5, Alison A Motsinger-Reif2,3,6, Howard L McLeod1,2,3,4. 1. 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. 2. UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA. 3. Pharmacogenetics for Every Nation Initiative, Chapel Hill, NC, USA. 4. Moffitt Cancer Center, DeBartolo Family Personalized Medicine Institute, Tampa, FL, USA. 5. Gentris Corporation, 133 Southcenter Ct, Morrisville, NC 27560, USA. 6. Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC 27695, USA.
Abstract
AIM: 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. METHODS & 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. CONCLUSION: 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.
AIM: 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. METHODS & 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. CONCLUSION: 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: Willy Albert Flegel; Kshitij Srivastava; Tristan Michael Sissung; Barry Ronald Goldspiel; William Douglas Figg Journal: Vox Sang Date: 2020-09-30 Impact factor: 2.996
Authors: Gurpreet S Ghattaoraya; Yenal Dundar; Faviel F González-Galarza; Maria Helena Thomaz Maia; Eduardo José Melo Santos; Andréa Luciana Soares da Silva; Antony McCabe; Derek Middleton; Ana Alfirevic; Rumona Dickson; Andrew R Jones Journal: Database (Oxford) Date: 2016-05-17 Impact factor: 3.451