The Pharmacogenomic HLA Biomarker Associated to Adverse Abacavir Reactions: Comparative Analysis of Different Genotyping Methods

Abstract

Many pharmacogenomic biomarkers (PGBM) were identified and translated into clinical practice, affecting the usage of drugs via label updates. In this context, abacavir is one of the most brilliant examples of pharmacogenetic studies translated into clinical practice. Pharmacogenetic studies have revealed that abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir. Accordingly to these results the abacavir label has been modified: the European Medicines Agency (EMA) and the FDA recommend/suggested that the administration of abacavir must be preceded by a specific genotyping test.

Detection of HLA-B*57:01 By Real-Time PCR: Implementation into Routine Clinical Practice and Additional Validation Data

“…A number of different techniques with rapid time of response have been developed and are at the present available to detect the HLA-B*57:01 allele. In a recent article, Stocchi and collaborators provided an update on what is currently available in the field, outlining future science group the scientific and pharmacoeconomic pros and cons of such techniques [15]. In this regard, we have characterized a test in Q-PCR, which is a fast and direct method to amplify and analyze genomic DNA, and suggested that this test could be easily implemented into routine clinical practice, particularly in those laboratories already involved in detection of viral load and virus genotyping [16].…”

“…However, this technique is not always readily available; therefore, other molecular techniques with rapid turnaround times have recently been developed to quickly detect the HLA-B*57:01 allele. These approaches are mostly based on sequence specific primers (SSPs) or oligonucleotide probes (as reviewed by Stocchi [15]). …”

High Frequency of Human Leukocyte Antigen-B*57:01 Allele Carriers among HIV-Infected Patients in Serbia

“…This is partly due to the mechanism underlying abacavirinduced HSR, which is explained by steric binding of the drug to the HLA-B * 57: 01 protein by specific amino-acid residues in its "F-pocket," resulting in the protein complexing with self-peptides, of which some become recognized as foreign [7,8] . A similar mechanism is speculated to be implicated in other drug-induced HLA-associated hypersensitivity [18,19] . However, abacavir HLA-B * 57: 01 penetrance was not absolute and possibly linked to differing spectrums of self-tolerant peptides in the different populations.…”

“…Nowadays, a number of high-resolution molecular techniques are being used for the detection of the HLA-B * 57: 01 allele, including sequence-specific oligonucleotide probe hybridization, DNA sequence-based typing, sequencespecific primer PCR, flow cytometry, allele-specific PCR, and real-time PCR [19] . In our study, we used commercially available real-time PCR, which is considered a fast and reliable method to accurately amplify and analyze genomic DNA [19] .…”

Review of nutrient actions on age-related macular degeneration

“…Knowledge on the molecular pathways of nutrients, according to the genetic identity of the patients, will enable the application of the most optimal treatment for each patient with AMD. Genetic profiling would likely contribute to our understanding of AMD and potentially provide more effective management of the disease, such as the case in HIV [89,90] and HCV [91,92] infection.…”