Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection
The HLA-B*58:01 allele has been identified as a genetic marker in the fatal allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, the screening of the HLA-B*58:01 allele prior to allopurinol prescription h...
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doaj-a0306387e2de4116bd066cfc633601d72021-03-30T04:43:28ZengIEEEIEEE Access2169-35362020-01-01822530622532310.1109/ACCESS.2020.30445629293282Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions DetectionKok Beng Gan0https://orcid.org/0000-0002-8776-5502Kim Soon Chong1https://orcid.org/0000-0002-0584-3010Anusha Devi Nawoor2Sue-Mian Then3https://orcid.org/0000-0001-7666-934XNor Azian Abdul Murad4A. Rahman A. Jamal5Department of Electrical, Electronic, and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia (UKM), Bangi, MalaysiaDepartment of Electrical, Electronic, and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia (UKM), Bangi, MalaysiaDivision of Biomedical Sciences, Faculty of Science and Engineering, University of Nottingham, Malaysia Campus, Semenyih, MalaysiaDivision of Biomedical Sciences, Faculty of Science and Engineering, University of Nottingham, Malaysia Campus, Semenyih, MalaysiaUKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia (UKM), Jalan Ya’acob Latiff, Kuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia (UKM), Jalan Ya’acob Latiff, Kuala Lumpur, MalaysiaThe HLA-B*58:01 allele has been identified as a genetic marker in the fatal allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, the screening of the HLA-B*58:01 allele prior to allopurinol prescription has not been implemented in hospitals, mostly due to the absence of an inexpensive and rapid screening method. In this work, we have developed a HLA-B*58:01 allele screening system which is able to give results in one and a half hour and is cheaper than any other screening instruments available. The system uses the High-Resolution Melt (HRM) method and generates difference melt curves proportional to a specific DNA's sequence. A positive screening result will be shown if the HLA-B*58:01 allele is detected in unknown samples screened. Twelve HRM experiments were performed to optimize the system and six final optimized experiments are shown in this article, along with their difference melt curves. The system was successfully benchmarked against the Illumina Eco Real Time machine and results were also validated by Sanger sequencing. The system was also compared against other HLA screening methods available on the market. We propose that the implementation of this HLA-B*58:01 screening system in hospitals will help to decrease the number of SCARs cases and eventually eliminate them in the long run. Patients will thus be prescribed allopurinol only if they test negative for the HLA-B*58:01 gene and those who test positive will be given alternative drugs, ultimately saving lives, time of treatment and overall medical cost.https://ieeexplore.ieee.org/document/9293282/Polymerase chain reactionhigh resolution meltingHLA-B*58:01 allelesevere cutaneous adverse reactions (SCARs)difference melt curve |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kok Beng Gan Kim Soon Chong Anusha Devi Nawoor Sue-Mian Then Nor Azian Abdul Murad A. Rahman A. Jamal |
spellingShingle |
Kok Beng Gan Kim Soon Chong Anusha Devi Nawoor Sue-Mian Then Nor Azian Abdul Murad A. Rahman A. Jamal Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection IEEE Access Polymerase chain reaction high resolution melting HLA-B*58:01 allele severe cutaneous adverse reactions (SCARs) difference melt curve |
author_facet |
Kok Beng Gan Kim Soon Chong Anusha Devi Nawoor Sue-Mian Then Nor Azian Abdul Murad A. Rahman A. Jamal |
author_sort |
Kok Beng Gan |
title |
Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection |
title_short |
Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection |
title_full |
Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection |
title_fullStr |
Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection |
title_full_unstemmed |
Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection |
title_sort |
development of a hla-b*58:01 allele screening system for allopurinol-induced severe cutaneous adverse reactions detection |
publisher |
IEEE |
series |
IEEE Access |
issn |
2169-3536 |
publishDate |
2020-01-01 |
description |
The HLA-B*58:01 allele has been identified as a genetic marker in the fatal allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, the screening of the HLA-B*58:01 allele prior to allopurinol prescription has not been implemented in hospitals, mostly due to the absence of an inexpensive and rapid screening method. In this work, we have developed a HLA-B*58:01 allele screening system which is able to give results in one and a half hour and is cheaper than any other screening instruments available. The system uses the High-Resolution Melt (HRM) method and generates difference melt curves proportional to a specific DNA's sequence. A positive screening result will be shown if the HLA-B*58:01 allele is detected in unknown samples screened. Twelve HRM experiments were performed to optimize the system and six final optimized experiments are shown in this article, along with their difference melt curves. The system was successfully benchmarked against the Illumina Eco Real Time machine and results were also validated by Sanger sequencing. The system was also compared against other HLA screening methods available on the market. We propose that the implementation of this HLA-B*58:01 screening system in hospitals will help to decrease the number of SCARs cases and eventually eliminate them in the long run. Patients will thus be prescribed allopurinol only if they test negative for the HLA-B*58:01 gene and those who test positive will be given alternative drugs, ultimately saving lives, time of treatment and overall medical cost. |
topic |
Polymerase chain reaction high resolution melting HLA-B*58:01 allele severe cutaneous adverse reactions (SCARs) difference melt curve |
url |
https://ieeexplore.ieee.org/document/9293282/ |
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