Design and implementation of a novel pharmacogenetic assay for the identification of the CYP2D6*10 genetic variant

Ranadeva, N. D. K.; Sirisena, Nirmala Dushyanthi; Wetthasinghe, Tithila Kalum; Noordeen, Nafeesa; Dissanayake, Vajira H. W.

doi:10.1186/s13104-022-05993-6

Cited by 4 publications

(1 citation statement)

References 20 publications

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“…They were recorded, and genotype frequencies for homozygous wild type (AA), heterozygous variant (AG), and homozygous variant (GG) genotypes, as well as allele frequencies for A (wild type) and G (variant) alleles, were calculated and tested for Hardy Weinberg equilibrium using an online calculator (available at: https://wpcalc.com/en/equilibrium-hardy-weinberg/). bands in terms of ideal concentrations of MgCl 2 , four primers, dNTPs and annealing temperature (22).…”

Section: Discussionmentioning

confidence: 99%

A Novel Tetra-Primer ARMS-PCR for genotyping of the OPRM 1 gene rs1779791 variant associated with opioid use disorders

Wijekumar¹,

Ranadeva²,

Jayamaha³

et al. 2023

Preprint

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Objectives: SNV is a single nucleotide change that can occur at any point in the genome. It is regarded as a frequent genetic variant that can result in genetic diseases. Discovering genetic variants in individuals is one of the most essential jobs of genetic research. Researchers genotype SNVs using TaqMan technology, DNA microarray, MALDI-TOF mass spectrometry, and automated sequencing which is expensive and time-consuming. The OPRM1 gene rs1799971 (A118G) has been identified for its association with Opioid use disorder (OUD). The present study focused in developing a single step identification test using Tetra-Primer Amplification Refractory Mutation System-PCR (T-ARMS-PCR) in order to detect the presence of SNV OPRM1 rs1799971 (A118G). The present research was performed to optimize the protocol for the designed four primers and validate using a total of 52 buccal samples from volunteers who are currently under rehabilitation for the drug abuse disorder. Results: The novel assay was successfully designed, tested, and validated using 52 DNA samples. The products of the T-ARMS PCR for rs1799971 contained 395bp as the control band, 186bp as G allele (variant) and 257bp as A allele (wild type) were observed in the gel image. The genotype frequencies for the OPRM1 gene rs1799971 (A118G) were 44% (22/52) of homozygous variant type (GG), 28.9% (15/52) of homozygous wild type (AA) and 28.9% (15/22) of heterozygous (AG). The minor allele (G) frequency was 56.7% and major allele (A) frequency was 43.3%.

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Section: Discussionmentioning

confidence: 99%

A Novel Tetra-Primer ARMS-PCR for genotyping of the OPRM 1 gene rs1779791 variant associated with opioid use disorders

Wijekumar¹,

Ranadeva²,

Jayamaha³

et al. 2023

Preprint

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Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications

Ranasinghe,

Jeyapragasam,

Liyanage

et al. 2024

Pharmacogenomics

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Frequency of pharmacogenomic variants affecting efficacy and safety of anti-cancer drugs in a south Asian population from Sri Lanka

Ranasinghe,

Sirisena,

Vishnukanthan

et al. 2024

BMC Med Genomics

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Background Therapy with anti-cancer drugs remain the cornerstone of treating cancer. The effectiveness and safety of anti-cancer drugs vary significantly among individuals due to genetic factors influencing the drug response and metabolism. Data on the pharmacogenomic variations in Sri Lankans related to anti-cancer therapy is sparse. As current treatment guidelines in Sri Lanka often do not consider local pharmacogenomic variants, this study aimed to explore the diversity of pharmacogenomic variants in the Sri Lankan population to pave the way for personalized treatment approaches and improve patient outcomes. Methods Pharmacogenomic data regarding variant-drug pairs of genes CYP2D6, DPYD, NUDT15, EPAS1, and XRCC1 with clinical annotations labelled as evidence levels 1A-2B were obtained from the Pharmacogenomics Knowledgebase database. Their frequencies in Sri Lankans were obtained from an anonymized database that was derived from 541 Sri Lankans who underwent exome sequencing at the Human Genetics Unit, Faculty of Medicine, University of Colombo. Variations in DPYD, NUDT15, and EPAS1 genes are related to increased toxicity to fluoropyrimidines, mercaptopurines, and sorafenib respectively. Variations in CYP2D6 and XRCC1 genes are related to changes in efficacy of tamoxifen and platinum compounds, respectively. Minor allele frequencies of these variants were calculated and compared with other populations. Results MAFs of rs1065852 c.100 C > T (CYP2D6), rs3918290 c.1905 + 1G > A (DPYD), rs56038477 c.1236G > A (DPYD), rs7557402 c.1035–7 C > G (EPAS1), rs116855232 c.415 C > T (NUDT15*3), and rs25487 c.1196 A > G (XRCC1) were: 12.9% [95%CI:10.9–14.9], 1.5% [95%CI:0.8–2.2], 1.2% [95%CI:0.5–1.8], 37.7% [95%CI:34.8–40.6], 8.3% [95%CI:6.7–10.0], and 64.0% [95%CI:61.1–66.8], respectively. Frequencies of rs1065852 c.100 C > T (CYP2D6), rs7557402 c.1035–7 C > G (EPAS1), and rs25487 (XRCC1) were significantly lower in Sri Lankans, while frequencies of rs116855232 c.415 C > T (NUDT15*3) and rs56038477 c.1236G > A (DPYD) were significantly higher in Sri Lankans when compared to some Western and Asian populations. Conclusion Sri Lankans are likely to show lower toxicity risk with sorafenib (rs7557402 c.84,131 C > G) and, higher toxicity risk with fluoropyrimidines (rs56038477 c.1236G > A) and mercaptopurine (rs116855232 c.415 C > T), and reduced effectiveness with tamoxifen (rs1065852 c.100 C > T) and platinum compounds (rs25487). These findings highlight the potential contribution of these genetic variations to the individual variability in anti-cancer dosage requirements among Sri Lankans.

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Design and implementation of a novel pharmacogenetic assay for the identification of the CYP2D6*10 genetic variant

Cited by 4 publications

References 20 publications

A Novel Tetra-Primer ARMS-PCR for genotyping of the OPRM 1 gene rs1779791 variant associated with opioid use disorders

A Novel Tetra-Primer ARMS-PCR for genotyping of the OPRM 1 gene rs1779791 variant associated with opioid use disorders

Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications

Frequency of pharmacogenomic variants affecting efficacy and safety of anti-cancer drugs in a south Asian population from Sri Lanka

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