The genomic landscape of CYP2D6 variation in the Indian population.
Pharmacogenomics
; 25(3): 147-160, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38426301
ABSTRACT
Aim:
The CYP2D6 gene is highly polymorphic, causing large interindividual variability in the metabolism of several clinically important drugs. Materials &methods:
The authors investigated the diversity and distribution of CYP2D6 alleles in Indians using whole genome sequences (N = 1518). Functional consequences were assessed using pathogenicity scores and molecular dynamics simulations.Results:
The analysis revealed population-specific CYP2D6 alleles (*86, *7, *111, *112, *113, *99) and remarkable differences in variant and phenotype frequencies with global populations. The authors observed that one in three Indians could benefit from a dose alteration for psychiatric drugs with accurate CYP2D6 phenotyping. Molecular dynamics simulations revealed large conformational fluctuations, confirming the predicted reduced function of *86 and *113 alleles.Conclusion:
The findings emphasize the utility of comprehensive CYP2D6 profiling for aiding precision public health.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocromo P-450 CYP2D6
/
Genômica
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article