Developing pharmacogenetic screening methods for an emergent country: Vietnam

Abstract

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.

A Novel Allele-Specific PCR Protocol for the Detection of the HLA-C*03:02 Allele, a Pharmacogenetic Marker, in Vietnamese Kinh People

“…A limitation of this protocol is time-consuming in comparison with other methods such as real-time PCR which requires approximately two hours. 23 Nevertheless, the total time for the test including DNA extraction is four hours, enabling to return genotyping results much earlier than sequencing by an outsourcing unit. In addition, this protocol does not require specially trained workers or expensive reagents and equipment; thus, it can be used for screening patients at risk of allopurinol-induced SCARs in local hospitals in developing countries.…”

“…The total cost for reagents in this method is less than $2, while the costs for high-throughput methods are usually higher. 23 Another limitation of this PCR-based protocol is the probability of false-positive results due to crosscontamination during electrophoresis or preparation of DNA template. The validation on 100 samples showed one sample with false-positive result (Table 3).…”

Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications

“…It has not been possible to accurately and non-invasively quantify the volume of topically used materials absorbed into the follicle. As a result, cyanoacrylate skin surface, stripping techniques, peel biopsy, etc., have been used to extract the topically applied dye-containing stratum corneum components and estimate the amount of drug absorbed through the transdermal route ( Nguyen et al, 2019 ). Different stripping techniques have also been applied to test the delivery of topically used products selectively and non-invasively into the follicular infundibula ( Desai et al, 2013 ; Nakkam et al, 2018 ; Carolina Oliveira Dos Santos et al, 2019 ).…”

Review on Databases and Bioinformatic Approaches on Pharmacogenomics of Adverse Drug Reactions

“…24,[42][43][44][45] Compared with next generation sequencing, this method is much cheaper and totally affordable for research, and it can be scaled and transformed into an application with little optimization. 46,47 Several genetic risk factors responding to drugs were discovered in the gene candidate approach. Abacavir becomes one of the first drugs studied to date to be aware by FDA in patients carrying HLA-B*57:01 alleles (released in 2017).…”