New pharmacogenetic test for detecting an HLA-A*31:01 allele using the InvaderPlus assay

Masayuki Aoki, Naoya Hosono, Sadaaki Takata, Yusuke Nakamura, Naoyuki Kamatani, Michiaki Kubo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Carbamazepine (CBZ) is widely used for the treatment of epilepsy and other neurological disorders. However, 3-5% of CBZ-treated individuals suffer from cutaneous adverse drug reactions (cADRs). Recently, in a genome-wide association study, HLA-A*31:01 has been reported to be a strong genetic marker for CBZ-induced cADRs in both Japanese and European populations. As most of the available methods for HLA genotyping are laborious, the development of a simple and rapid genotyping method for HLA-A*31:01 is desirable from the viewpoint of a clinical pharmacogenetic test. METHODS: More than 1700 sequences for HLA-A alleles were obtained from the MHC database of the National Center for Biotechnology Information (dbMHC). Several HLA-A*31:01-discriminating single-nucleotide polymorphisms were selected. These SNPs were used for sequence-specific primer PCR (SSP-PCR) and for the target site of the Invader reaction. By combining SSP-PCR with a target-specific Invader reaction, we designed two sets of primers/probes for HLA-A*31:01 allele detection. The performance of both sets was evaluated using 90 Asian HapMap samples. Further evaluation was carried out using another 376 Japanese samples and 90 CEU (European) and 90 YRI (African) HapMap samples. RESULTS: Our assay specifically detected an HLA-A*31:01 allele in a total of 466 individuals of the Asian population. Furthermore, the assay correctly identified HLA-A*31:01-positive carriers from the CEU and the YRI population, respectively, implying that the assay has potential for application to other ethnic groups. CONCLUSION: We developed a new HLA-A*31:01-detecting method by a combination of SSP-PCR with target-specific InvaderPlus technology. As our assay is rapid and accurate, it is hoped that this method will be used in a pharmacogenetic test in a clinical setting to avoid CBZ-induced cADRs.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
JournalPharmacogenetics and Genomics
Volume22
Issue number6
DOIs
Publication statusPublished - 01-06-2012
Externally publishedYes

Fingerprint

Pharmacogenetics
Alleles
Carbamazepine
Drug-Related Side Effects and Adverse Reactions
HapMap Project
Polymerase Chain Reaction
Skin
Single Nucleotide Polymorphism
Population
Information Centers
HLA-A Antigens
Genome-Wide Association Study
Biotechnology
HLA-A31 antigen
Nervous System Diseases
Genetic Markers
Ethnic Groups
Epilepsy
Databases
Technology

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Aoki, Masayuki ; Hosono, Naoya ; Takata, Sadaaki ; Nakamura, Yusuke ; Kamatani, Naoyuki ; Kubo, Michiaki. / New pharmacogenetic test for detecting an HLA-A*31:01 allele using the InvaderPlus assay. In: Pharmacogenetics and Genomics. 2012 ; Vol. 22, No. 6. pp. 441-446.
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abstract = "BACKGROUND & AIMS: Carbamazepine (CBZ) is widely used for the treatment of epilepsy and other neurological disorders. However, 3-5{\%} of CBZ-treated individuals suffer from cutaneous adverse drug reactions (cADRs). Recently, in a genome-wide association study, HLA-A*31:01 has been reported to be a strong genetic marker for CBZ-induced cADRs in both Japanese and European populations. As most of the available methods for HLA genotyping are laborious, the development of a simple and rapid genotyping method for HLA-A*31:01 is desirable from the viewpoint of a clinical pharmacogenetic test. METHODS: More than 1700 sequences for HLA-A alleles were obtained from the MHC database of the National Center for Biotechnology Information (dbMHC). Several HLA-A*31:01-discriminating single-nucleotide polymorphisms were selected. These SNPs were used for sequence-specific primer PCR (SSP-PCR) and for the target site of the Invader reaction. By combining SSP-PCR with a target-specific Invader reaction, we designed two sets of primers/probes for HLA-A*31:01 allele detection. The performance of both sets was evaluated using 90 Asian HapMap samples. Further evaluation was carried out using another 376 Japanese samples and 90 CEU (European) and 90 YRI (African) HapMap samples. RESULTS: Our assay specifically detected an HLA-A*31:01 allele in a total of 466 individuals of the Asian population. Furthermore, the assay correctly identified HLA-A*31:01-positive carriers from the CEU and the YRI population, respectively, implying that the assay has potential for application to other ethnic groups. CONCLUSION: We developed a new HLA-A*31:01-detecting method by a combination of SSP-PCR with target-specific InvaderPlus technology. As our assay is rapid and accurate, it is hoped that this method will be used in a pharmacogenetic test in a clinical setting to avoid CBZ-induced cADRs.",
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New pharmacogenetic test for detecting an HLA-A*31:01 allele using the InvaderPlus assay. / Aoki, Masayuki; Hosono, Naoya; Takata, Sadaaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kubo, Michiaki.

In: Pharmacogenetics and Genomics, Vol. 22, No. 6, 01.06.2012, p. 441-446.

Research output: Contribution to journalArticle

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T1 - New pharmacogenetic test for detecting an HLA-A*31:01 allele using the InvaderPlus assay

AU - Aoki, Masayuki

AU - Hosono, Naoya

AU - Takata, Sadaaki

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

PY - 2012/6/1

Y1 - 2012/6/1

N2 - BACKGROUND & AIMS: Carbamazepine (CBZ) is widely used for the treatment of epilepsy and other neurological disorders. However, 3-5% of CBZ-treated individuals suffer from cutaneous adverse drug reactions (cADRs). Recently, in a genome-wide association study, HLA-A*31:01 has been reported to be a strong genetic marker for CBZ-induced cADRs in both Japanese and European populations. As most of the available methods for HLA genotyping are laborious, the development of a simple and rapid genotyping method for HLA-A*31:01 is desirable from the viewpoint of a clinical pharmacogenetic test. METHODS: More than 1700 sequences for HLA-A alleles were obtained from the MHC database of the National Center for Biotechnology Information (dbMHC). Several HLA-A*31:01-discriminating single-nucleotide polymorphisms were selected. These SNPs were used for sequence-specific primer PCR (SSP-PCR) and for the target site of the Invader reaction. By combining SSP-PCR with a target-specific Invader reaction, we designed two sets of primers/probes for HLA-A*31:01 allele detection. The performance of both sets was evaluated using 90 Asian HapMap samples. Further evaluation was carried out using another 376 Japanese samples and 90 CEU (European) and 90 YRI (African) HapMap samples. RESULTS: Our assay specifically detected an HLA-A*31:01 allele in a total of 466 individuals of the Asian population. Furthermore, the assay correctly identified HLA-A*31:01-positive carriers from the CEU and the YRI population, respectively, implying that the assay has potential for application to other ethnic groups. CONCLUSION: We developed a new HLA-A*31:01-detecting method by a combination of SSP-PCR with target-specific InvaderPlus technology. As our assay is rapid and accurate, it is hoped that this method will be used in a pharmacogenetic test in a clinical setting to avoid CBZ-induced cADRs.

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