Identification and drug metabolic activity evaluation of 12 CYP2D6 allelic variants newly detected in the Chinese population.

Novel CYP2D6 alleles with reduced enzymatic activity in the Chinese Han population

Among 1,211 Chinese Han individuals genotyped by multiplex amplicon sequencing, 12 novel CYP2D6 allelic variants were identified and functionally characterized by recombinant expression in insect microsomes with enzyme kinetics. Variants R221C, L224P, and P268R showed reduced activity toward dextromethorphan; R32H, R221C, R259S, and P268R displayed impaired metoprolol metabolism. No differences in protein expression were observed by Western blot, suggesting direct functional impact on catalytic activity. These data allow more accurate CYP2D6 phenotype assignment in the Han population.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

CYP2D6 is one of the most polymorphic pharmacogenes, and the identification of 12 novel alleles with functional characterization on two CPIC reference substrates is a genuine contribution to PharmVar annotation. These data are particularly relevant for PGx laboratories genotyping patients of Asian descent, a population whose allelic coverage remains incomplete in current commercial panels.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Journal quality: 0/1 → Total: 7/10