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- W4328118700 abstract "The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function ( CYP2C19*2 and CYP2C19 * 3 ), reduced function ( CYP2C19*9) and increased function ( CYP2C19*1 7) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17 . We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014—to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19- predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype." @default.
- W4328118700 created "2023-03-22" @default.
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- W4328118700 date "2023-03-21" @default.
- W4328118700 modified "2023-10-14" @default.
- W4328118700 title "Distribution of a novel CYP2C haplotype in Native American populations" @default.
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- W4328118700 doi "https://doi.org/10.3389/fgene.2023.1114742" @default.
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