Accuracy of SNPs to predict risk of HLA alleles associated with drug-induced hypersensitivity events across racial groups

Yijing He; Janelle M Hoskins; Scott Clark; Nathan H Campbell; Kim Wagner; Alison A Motsinger-Reif; Howard L McLeod

doi:10.2217/pgs.15.41

Accuracy of SNPs to predict risk of HLA alleles associated with drug-induced hypersensitivity events across racial groups

Pharmacogenomics. 2015 Jul;16(8):817-24. doi: 10.2217/pgs.15.41. Epub 2015 Jun 17.

Authors

Yijing He^{1

2

3

4}, Janelle M Hoskins⁵, Scott Clark⁵, Nathan H Campbell⁵, Kim Wagner⁵, Alison A Motsinger-Reif^{2

3

6}, Howard L McLeod^{1

2

3

4}

Affiliations

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.

PMID: 26083016
DOI: 10.2217/pgs.15.41

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.

Keywords: HLA; drug-induced hypersensitivity; human leukocyte antigen; pharmacogenetics; pharmacogenomics; risk mitigation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Asian People / genetics
Black or African American / genetics
Drug Hypersensitivity / genetics*
Drug Hypersensitivity / pathology
Genotype
HLA-B Antigens / genetics*
HLA-DQ alpha-Chains / genetics*
Hispanic or Latino / genetics
Humans
Polymorphism, Single Nucleotide / genetics*
White People

Substances

HLA-B Antigens
HLA-B57 antigen
HLA-DQ alpha-Chains
HLA-DQA1 antigen