Pharmacogenomic diversity in Singaporean populations and Europeans

Abstract

Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.

Analysis of Genetic Variation in CYP450 Genes for Clinical Implementation

“…In line with previous findings, CYP3A5*3 is prevalent in our population with allele frequencies ranging from 0.587 to 0.734 [26]. VKORC1*2 differed by approximately 5 folds within our population.…”

“…Overall, the allelic frequencies were similar to those reported in the ExAC database (East Asian—Chinese and Malay; South Asian—Indian). Five different alleles of CYP2C9 were examined and the frequencies of the defective alleles *2 and *3 found in our study were comparable with published data [26]. The *3 allele was more common in our population whereas *2 allele is only observed in the Indians with a frequency of 0.042.…”

Polimorfismo Val/Met en gen OCT1 de respuesta a metformina en muestras de Lima y Puno. Enfoque farmacogenético de la diabetes

“…La respuesta individual depende del perfi l genéti co de la persona y es infl uenciada por su origen étnico. Por tanto, son factores importantes para la toma de decisiones en la clínica y tratamiento de las enfermedades (2) .…”

“…Los polimorfi smos en diversos genes pueden explicar la variabilidad en la respuesta farmacológica. Por lo tanto, si se conoce la farmacogenéti ca, las evaluaciones de riesgo serán más precisas y mejora la toma de decisiones (1,2) . La diabetes mellitus ti po 2 (DMT2) es una enfermedad multi factorial, es decir, intervienen factores ambientales y genéti cos predisponentes (3) .…”

Inclusion of Indigenous Australians in biobanks: a step to reducing inequity in health care

“…Concerns about the diversity of biobanks are not limited to ethical uncertainties regarding inclusivity. The misclassification of benign variants as pathogenic has led to genetic misdiagnoses for specific racial groups, and specific genetic variants across unique populations have been shown to affect drug metabolism, resulting in an ineffective or adverse effect . Therefore, the inclusion of minority groups within biobanks is not just an ethical obligation but a requirement for genomic advances that translate to the broader population.…”