Carbamazepine-induced cutaneous reactions: A simple assay to identify patients carrying the <i>HLA-A*31:01</i> allele

Thorstensen, Ketil; Kvitland, Mona; Shirzadi, Maryam; Helde, Grethe; Moen, Torolf; Brodtkorb, Eylert

doi:10.3109/00365513.2014.921835

Cited by 7 publications

(6 citation statements)

References 10 publications

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“…Across all ancestral groups in which rs1061235 was identified, the r 2 value was 1.000. Thorstensen et al (2014) used a polymerase chain reaction-restriction fragment length polymorphism assay to investigate rs1061235 as a tag for HLA-A*31:01 in Norwegians. In a set of 204 samples, their assay had 100% sensitivity and 99.5% specificity for tagging HLA-A*31:01 .…”

Section: Resultsmentioning

confidence: 99%

“…The assay performs best when the number of PCR amplification cycles is increased to 50 (increasing total run time from 90 to 110 min). Assay ANNK49J for rs1061235 also identified HLA-A*31:01 with 100% sensitivity, with its specificity impacted by this SNV also being present in the HLA-A*33:01 and HLA-A*33:03 haplotypes ( Thorstensen et al, 2014 ). A study in an ancestrally-diverse group of Canadian children ( Amstutz et al, 2013 ) found that out of 20 children carrying the minor allele of rs1061235, 12 had a haplotype of HLA-A*31:01 , five had a haplotype of HLA-A*33:03 , and three had a haplotype of HLA-A*33:01 .…”

Section: Discussionmentioning

confidence: 99%

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Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B15:02 and HLA-A31:01 Across Diverse Ancestral Backgrounds

Buchner

Aitchison

2021

Front. Pharmacol.

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The human leukocyte antigen haplotypes HLA-B*15:02 and HLA-A*31:01 have been linked to life-threatening adverse drug reactions to the anticonvulsants carbamazepine and oxcarbazepine. Identification of these haplotypes via pharmacogenetic techniques facilitates implementation of precision medicine to prevent such reactions. Using reference samples from diverse ancestral origins, we investigated the test analytical validity (i.e., ability to detect whether or not the haplotypes were present or absent) of TaqMan assays for single nucleotide variants previously identified as potentially being able to “tag” these haplotypes. A TaqMan custom assay for rs10484555 and an inventoried assay for rs17179220 and were able to identify with 100% sensitivity and 100% specificity HLA-B*15:02 and HLA-A*31:01 respectively. A custom assay for rs144012689 that takes into account a neighboring single nucleotide variant with manual calling was also able to identify HLA-B*15:02 with 100% sensitivity and 100% specificity. A custom assay for rs106235 identified HLA-A*31:01 with 100% sensitivity and 95% specificity. The slight reduction in specificity for the latter was owing to another haplotype (HLA-A*33:03) also being detected. While any positive call using the rs106235 assay could therefore be further investigated, as the presence of the HLA-A*31:01 haplotype confers adverse drug reaction risk, the absence of false negatives (indexed by sensitivity) is more important than false positives. In summary, we present validated TaqMan assay methodology for efficient detection of HLA haplotypes HLA-B*15:02 and HLA-A*31:01. Our data are relevant for other genotyping technologies that identify, or have the potential to identify, these haplotypes using single nucleotide variants.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B15:02 and HLA-A31:01 Across Diverse Ancestral Backgrounds

Buchner

Aitchison

2021

Front. Pharmacol.

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“…High risk of a false positive result by cross-contamination during the second PCR.PCR-RFLPrs1061235 linked to HLA-B*31:01Thorstensen et al. 2014 77 RapidCheapThe method has be applied in certain populations (the Norwegian population). For other populations, validation is needed.…”

Section: Hla and Hla Typing Methods For Hla Screeningmentioning

confidence: 99%

“…It is, however, a potential candidate for utilization in HLA screening due to its simplicity and cost-effectiveness 74 . Currently, there are a number of single nucleotide polymorphisms (SNPs) which have been reported as potential surrogate markers, based on their linkage disequilibrium (LD) for detection of HLA-B*15:02, 75 HLA-B*58:01 76 and HLA-A*31:01, 77 HLA-B*57:0178, 79 Heterogeneity has been observed, however, across different populations 80 . For example, a haplotype of two SNPs, rs2844682C > T and rs3903184C > G, was proposed as a surrogate marker for HLA-B*15:02 in Han Chinese, 75 although later work refuted this finding 81 , and rs9263726 A > G has been found to be tightly linked with HLA-B*58:01 in Japanese 15 and Chinese 82 but not Australians 83 .…”

Section: Hla and Hla Typing Methods For Hla Screeningmentioning

confidence: 99%

Developing pharmacogenetic screening methods for an emergent country: Vietnam

Nguyen¹,

Vidal²,

Chu³

et al. 2019

World Allergy Organization Journal

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Background The finding of strong associations between certain human leukocyte antigen (HLA) genotypes and the development of severe cutaneous adverse drug reactions (SCARs), [for example, HLA-B*57:01 and abacavir (ABC), HLA-B*15:02 and carbamazepine (CBZ) and HLA-B*58:01 and allopurinol], has led to HLA screening being used to prevent SCARs. Screening has been shown to be of great benefit in a number of studies. Clinical translation from bench to bedside, however, depends upon the development of simple, rapid and cost-effective assays to detect these risk alleles. In highly populated developing countries such as Vietnam, where there is a high prevalence of HLA-B*15:02 and HLA-B*58:01 correlating with a high incidence of CBZ- and allopurinol-induced SCARs, the crucial factor in the implementation of comprehensive screening programs to detect these major risk HLA alleles is the availability of suitable assays. Body We have summarized the role and economic benefits of HLA screening, reviewed published HLA screening methods used currently in pharmacogenetic screening and examined the advantages and disadvantages of assays developed specifically for use in screening for risk alleles in the prevention of HLA-associated SCARs in Vietnam. Conclusion The optimal approach we propose may serve as a template for the development of screening programs in other emergent countries.

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“…However, the recent assays proposed for the screening test are only able to detect the HLA‐B*15:02 allele or the HLA‐A*31:01 allele, separately. Consequently, this can raise the cost and time requirement for performing the screening test.…”

Section: Introductionmentioning

confidence: 99%

A novel multiplex polymerase chain reaction assay for detection of both HLA‐A31:01/HLA‐B15:02 alleles, which confer susceptibility to carbamazepine‐induced severe cutaneous adverse reactions

Nguyen

Vidal

et al. 2017

HLA

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HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/μL. The unit cost of this assay is less than $5 USD with total time of 110 minutes.

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Carbamazepine-induced cutaneous reactions: A simple assay to identify patients carrying the HLA-A31:01* allele

Abstract: We have designed and validated a simple, fast and inexpensive test for the rs1061235A> T SNP as a marker for HLA-A*31:01 in the Norwegian population for potential use in a personalized treatment approach to patients planned to receive CBZ.

Cited by 7 publications

References 10 publications

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B15:02 and HLA-A31:01 Across Diverse Ancestral Backgrounds

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B15:02 and HLA-A31:01 Across Diverse Ancestral Backgrounds

Developing pharmacogenetic screening methods for an emergent country: Vietnam

A novel multiplex polymerase chain reaction assay for detection of both HLA‐A31:01/HLA‐B15:02 alleles, which confer susceptibility to carbamazepine‐induced severe cutaneous adverse reactions

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Carbamazepine-induced cutaneous reactions: A simple assay to identify patients carrying the HLA-A*31:01 allele

Abstract: We have designed and validated a simple, fast and inexpensive test for the rs1061235A> T SNP as a marker for HLA-A*31:01 in the Norwegian population for potential use in a personalized treatment approach to patients planned to receive CBZ.

Cited by 7 publications

References 10 publications

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B*15:02 and HLA-A*31:01 Across Diverse Ancestral Backgrounds

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B*15:02 and HLA-A*31:01 Across Diverse Ancestral Backgrounds

Developing pharmacogenetic screening methods for an emergent country: Vietnam

A novel multiplex polymerase chain reaction assay for detection of both HLA‐A*31:01/HLA‐B*15:02 alleles, which confer susceptibility to carbamazepine‐induced severe cutaneous adverse reactions

Contact Info

Product

Resources

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Carbamazepine-induced cutaneous reactions: A simple assay to identify patients carrying the HLA-A31:01* allele

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B15:02 and HLA-A31:01 Across Diverse Ancestral Backgrounds

Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B15:02 and HLA-A31:01 Across Diverse Ancestral Backgrounds

A novel multiplex polymerase chain reaction assay for detection of both HLA‐A31:01/HLA‐B15:02 alleles, which confer susceptibility to carbamazepine‐induced severe cutaneous adverse reactions