Pharmacogenomics of thiopurines: distribution of TPMT and NUDT15 polymorphisms in the Brazilian Amazon
This study evaluated the influence of Native ancestry on the distribution of TPMT (rs1142345, rs1800460 and rs1800462) and NUDT15 (rs116855232) polymorphisms and compound metabolic phenotypes in 128 healthy males from the Brazilian Amazon. The average proportion of Native and European ancestry differed greatly and significantly between self-declared Amerindians and non-Amerindians, although extensive admixture in both groups was evident. Native ancestry was not significantly associated with the frequency distribution of the TPMT or NUDT15 polymorphisms investigated. The apparent discrepancy with our previous results for NU...
Source: Pharmacogenetics and Genomics - September 4, 2020 Category: Genetics & Stem Cells Tags: Short Communication Source Type: research
Cost-effectiveness analysis of pretreatment screening for NUDT15 defective alleles
Conclusion
With a low cost-effectiveness threshold, combined screening for NUDT15 and TPMT defective alleles is cost-effective compared to TMPT screening alone in patients of Asian descent, but is unrealistic from a cost-effectiveness point of view in Caucasians. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - September 4, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Abacavir adverse reactions related with HLA-B*57:01 haplotype in a large cohort of patients infected with HIV
Conclusion
Not all abacavir-related side effects occur as a result of classic HLA-B*57:01-mediated hypersensitivity reaction, as they can develop irrespective of HLA-B*57:01 status. Clinical vigilance must be an essential part of the management of individuals starting abacavir, at any time during treatment. In a ‘real-life’ setting, clinical diagnosis of suspected abacavir hypersensitivity reaction in allele non-carriers remains crucial for further clinical decision making. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - September 4, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria
Plasmodium vivax has the largest geographic range of human malaria species and is challenging to manage and eradicate due to its ability to establish a dormant liver stage, the hypnozoite, which can reactivate leading to relapse. Until recently, the only treatment approved to kill hypnozoites was the 8-aminoquinoline, primaquine, requiring daily treatment for 14 days. Tafenoquine, an 8-aminoquinoline single-dose treatment with activity against P. vivax hypnozoites, has recently been approved by the US Food and Drug Administration and Australian Therapeutic Goods Administration for the radical cure of P. vivax malaria in ...
Source: Pharmacogenetics and Genomics - August 13, 2020 Category: Genetics & Stem Cells Tags: Short Communication Source Type: research
HLA-B*58:01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia
Objective
The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined.
Methods
We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and on...
Source: Pharmacogenetics and Genomics - August 13, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Use of antidepressants with pharmacogenetic prescribing guidelines in a 10-year depression cohort of adult primary care patients
Conclusion
One-quarter of primary care patients used an antidepressant that was not recommended for them based on CYP2D6- and CYP2C19-based prescribing guidelines and switching medications tended to be more common in this group. Studies to determine the impact of CYP2D6 and CYP2C19 genotyping on reducing gene-antidepressant mismatches are warranted. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - August 13, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
Conclusion
Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - July 30, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Effects of KCNMB2 gene polymorphisms on ritodrine therapy outcomes in women with preterm labor
Conclusion
This pharmacogenomic study suggests that ritodrine efficacy and ADEs are associated with KCNMB2 gene polymorphisms in patients with preterm labor. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - July 30, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
The effect of SLC6A3 variable number of tandem repeats and methylation levels on individual susceptibility to start tobacco smoking and on the ability of smokers to quit smoking
Conclusion
The SLC6A3 5R of 30 bp and 9R of 40 bp VNTR variants may lead to a reduced risk to start smoking through decreased dopamine availability, and can also affect the success in subsequent smoking cessation attempts. Moreover, the elevated mean methylation values in the first intron of SLC6A3 may be related to nicotine dependence via a more active dopamine transporter. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - July 30, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Cis-acting regulatory elements regulating CYP3A4 transcription in human liver
This study aims to identify cis-acting regulatory elements controlling the transcription of CYP3A4, using chromatin conformation capture (4C and 3C assays), chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR), clustered regularly interspaced short palindromic repeats (CRISPR)-mediated deletions of genomic regions and reporter gene assays in primary culture human hepatocytes and hepatic cell lines. 4C assays identified four regions (R1–R4) interacting with the CYP3A4 promoter, one of which overlaps with the previously identified upstream enhancers CLEM4/XREM (R2) while the other three are novel. ChIP-qP...
Source: Pharmacogenetics and Genomics - June 6, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Influence of selected polymorphisms in disposition genes on lumefantrine pharmacokinetics when coadministered with efavirenz
Conclusion
The findings revealed that the efavirenz–lumefantrine interaction was accentuated in the group with CYP2B6 c.516T, c.983C and NR1I3 152c-1089T alleles. This warrants further investigations of other drug–drug interactions for optimising dosing in genetically defined subgroups, particularly during drug development. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - June 6, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Identification of populations likely to benefit from pharmacogenomic testing
Conclusion
We demonstrate a significant number of patients in each group may have benefit, but targeting certain ones for pre-emptive testing may result in the initial highest yield for a health system. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - June 6, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
PharmGKB summary: lamotrigine pathway, pharmacokinetics and pharmacodynamics
No abstract available (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - May 1, 2020 Category: Genetics & Stem Cells Tags: PharmGKB Summary Source Type: research
Knowledge, attitude, and practice towards pharmacogenomics among hospital pharmacists in Thailand
Background and objectives
Pharmacogenomics (PGx) is the use of human genomic information to avoid toxicity and optimize efficacy of drug therapy in an individual. Hospital pharmacists are the key persons to facilitate the incorporation of PGx into clinical practice. PGx is relatively new to Thai hospital pharmacists. Therefore, this study aimed to evaluate the knowledge, attitude, and practice of Thai hospital pharmacists towards PGx implementation.
Materials and methods
We conducted a cross-sectional questionnaire-based survey among 600 hospital pharmacists in 21 hospitals across Thailand. The questionnaire consisted...
Source: Pharmacogenetics and Genomics - May 1, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Distribution and linkage disequilibrium of the enhancer SNP rs5758550 among Latin American populations: influence of continental ancestry
We examined the influence of individual biogeographical ancestry on the frequency distribution of rs5758550 and its LD with rs16947 in Latin American populations. We then inferred the impact of rs5758550 on the predictive accuracy of CYP2D6 metabolizer status based on CYP2D6 haplotypes.
Methods
The study cohorts consisted of the Admixed American (AMR) superpopulation of the 1000 Genomes Project (n = 347) plus an admixed Brazilian (BR) cohort (N = 224). Individual proportions of Native, African and European ancestry estimated by ADMIXTURE analysis, were used to design four sub-cohorts, in which one of the three ancestral...
Source: Pharmacogenetics and Genomics - May 1, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
