Abstract
Differences in drug responses in individuals are partly due to genetic variations in pharmacogenes, which differ among populations. Here, genome sequencing of 171 unrelated Thai individuals from all regions of Thailand was used to call star alleles of 51 pharmacogenes by Stargazer, determine allele and genotype frequencies, predict phenotype and compare high-impact variant frequencies between Thai and other populations. Three control genes, EGFR, VDR, and RYR1, were used, giving consistent results. Every individual had at least three genes with variant or altered phenotype. Forty of the 51 pharmacogenes had at least one individual with variant or altered phenotype. Moreover, thirteen genes had at least 25% of individuals with variant or altered phenotype including SLCO1B3 (97.08%), CYP3A5 (88.3%), CYP2C19 (60.82%), CYP2A6 (60.2%), SULT1A1 (56.14%), G6PD (54.39%), CYP4B1 (50.00%), CYP2D6 (48.65%), CYP2F1 (46.41%), NAT2 (40.35%), SLCO2B1 (28.95%), UGT1A1 (28.07%), and SLCO1B1 (26.79%). Allele frequencies of high impact variants from our samples were most similar to East Asian. Remarkably, we identified twenty predicted high impact variants which have not previously been reported. Our results provide information that contributes to the implementation of pharmacogenetic testing in Thailand and other Southeast Asian countries, bringing a step closer to personalized medicine.
Highlights
Genetic variations play an important role in personalized drug response and constitute pharmacogenetics biomarkers for drug dosing, effectiveness, and toxicity [1]
In an effort to determine the star allele profile for a more comprehensive list of relevant and meaningful pharmacogenes in a general Thai population, this study explored allele frequencies, genotype frequencies, phenotype prediction together with deleterious variants in 51 pharmacogenes using WGS data of 171 unrelated healthy Thai individuals from all geographical regions of Thailand
Geographical areas were available from 65.5% of participants and showed that they were from all regions of Thailand (S1 Table in S2 File)
Summary
Genetic variations play an important role in personalized drug response and constitute pharmacogenetics biomarkers for drug dosing, effectiveness, and toxicity [1]. A meta-analysis of 56,945 individuals studying allele frequencies of 12 CYP genes in several ethnicities, but only 7.6% were data of East Asians [2]. High-throughput DNA sequencing technologies with decreasing costs lead genome and exome sequencing to be increasingly used in clinical medicine. They provide the molecular diagnosis for the primary disease and offer a determination of genetic variations in pharmacogenes. In an effort to determine the star allele profile for a more comprehensive list of relevant and meaningful pharmacogenes in a general Thai population, this study explored allele frequencies, genotype frequencies, phenotype prediction together with deleterious variants in 51 pharmacogenes using WGS data of 171 unrelated healthy Thai individuals from all geographical regions of Thailand
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