alexa CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure.
Medicine

Medicine

Emergency Medicine: Open Access

Author(s): Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G,

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Abstract BACKGROUND AND OBJECTIVE: CYP2D6, a member of the cytochrome P450 superfamily, is responsible for the metabolism of about 25\% of the commonly prescribed drugs. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of medication or therapeutic failure with recommended drug dosages. This study aimed to describe the CYP2D6 diversity at the global level. METHODS: A total of 1060 individuals belonging to 52 worldwide-distributed populations were genotyped at 12 highly informative variable sites, as well as for gene deletion and duplications. Phenotypes were predicted on the basis of haplotype combinations. RESULTS AND CONCLUSIONS: Our study shows that (i) CYP2D6 diversity is far greater within than between populations and groups thereof, (ii) null or low-activity variants occur at high frequencies in various areas of the world, (iii) linkage disequilibrium is lowest in Africa and highest in the Americas. Patterns of variation, within and among populations, are similar to those observed for other autosomal markers (e.g. microsatellites and protein polymorphisms), suggesting that the diversity observed at the CYP2D6 locus reflects the same factors affecting variation at random genome markers. This article was published in Pharmacogenet Genomics and referenced in Emergency Medicine: Open Access

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