Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness

Abstract

Interethnic variability in drug response arises from genetic differences associated with drug metabolism, action and transport. These genetic variations can affect drug efficacy as well as cause adverse drug reactions (ADRs). We retrieved drug-response related single nucleotide polymorphism (SNP) associated data from databases and analyzed to elucidate population specific distribution of 159 drug-response related SNPs in twenty six populations belonging to five super-populations (African, Admixed Americans, East Asian, European and South Asian). Significant interpopulation differences exist in the minor (variant) allele frequencies (MAFs), linkage disequilibrium (LD) and haplotype distributions among these populations. 65 of the drug-response related alleles, which are considered as minor (variant) in global population, are present as the major alleles (frequency �0.5) in at least one or more populations. Populations that belong to the same super-population have similar distribution pattern for majority of the variant alleles. These drug response related variant allele frequencies and their pairwise LD measure (r 2) can clearly distinguish the populations in a way that correspond to the known evolutionary history of human and current geographic distributions, while D' cannot. The data presented here may aid in identifying drugs that are more appropriate and/or require pharmacogenetic testing in these populations. Our findings emphasize on the importance of distinct, ethnicity-specific clinical guidelines, especially for the African populations, to avoid ADRs and ensure effective drug treatment.

Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations

“…The presence of significant interethnic differences in the PGx biomarker allele frequencies were confirmed by analyzing individuals from different world populations (60)(61)(62)(63). Findings that there are remarkable differences in allele frequencies in PGx markers in different geographic areas could be of importance for developing ethnicity-specific guidelines for medical prioritization as well as preemptive testing, especially for the African populations (58,60). For ethnically diverse populations the identification of subpopulations with an increased risk of ADRs is also needed (64).…”

<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

“…This model describes an early stage (stage I), coinciding with incubation and/or mild flulike symptoms, during which antiviral drugs might reach high effectiveness, a moderate stage (stage II) characterized by pulmonary involvement without IIa or with IIb hypoxia, which may benefit from the use of antivirals and anti-inflammatory therapy (including steroids), and lastly a severe stage (stage III), in which a dysregulated, systemic hyperinflammatory response takes place, thus requiring the administration of immunomodulating agents, several of which are currently under investigation, and in some cases already in use within management protocols. 37 Gene variants associated with pharmacological responses to drugs are reported in a dedicated database -PharmGKB (https://www.pharmgkb.org) -allowing the identification of relationships between genetic variations (eg, SNPs, indels, repeats, haplotypes) and individual drug responsiveness. 40,41 Herein, in silico pharmacogenetic analysis shows the potential clinical efficacy and/or toxicity of the major drugs selected for Covid-19 treatment.…”

“…We considered SNPs related to both efficacy and toxicity response with allele frequencies ≥5%, as already described in previous studies. 36,37 The quality of each study was assured, and resulting information included study design, baseline characteristics of disease, treatment regimens, and allelic frequencies of the genetic variant.…”

Population structure and pharmacogenomic risk stratification in the United States

“…We posit that GA provides a number of advantages over racial/ethnic categories for biomedical research: (i) it can be characterized independently of the social and environmental dimensions of race/ethnicity, (ii) it can be measured objectively and with precision, and (iii) it can be quantified as a continuous variable, as opposed to categorical racial/ethnic labels. Indeed, a number of recent studies have focused on PGx variation among populations defined by GA rather than racial and ethnic groups [25][26][27][28][29][30][31].…”