Allelic diversity of the pharmacogene CYP2D6 in New Zealand Māori and Pacific peoples

The primary aim of this study was to investigate the allelic diversity of the pharmacogene CYP2D6 in a cohort of Māori and Pacific Island people in New Zealand. The study sought to characterize CYP2D6 variants in this underrepresented population, given that CYP2D6 is responsible for metabolising approximately 25% of commonly prescribed drugs, and genetic diversity in this gene can influence drug response and adverse reactions. The research aimed to address the lack of pharmacogenetic data for indigenous populations in Oceania.

Oxford Nanopore sequencing was used in this study to generate long sequencing reads of the CYP2D6 gene from 202 individuals. This sequencing approach allowed the team to capture the full-length gene and analyse genetic variations comprehensively, including upstream and downstream regulatory regions.

The major findings revealed 13 different CYP2D6 star alleles, including four novel alleles (*167, *168, *169, and *170) and 12 variants that had not been previously reported in the PharmVar database. Notably, the study found a relatively high frequency (8.9%) of the rare CYP2D6 *71 allele, which has uncertain functional effects. This allele had been previously identified in only a few other studies, predominantly in Asian populations. The study also found that 73% of the participants were classified as normal metabolizers, 8% as intermediate metabolizers, and no individuals were classified as ultrarapid or poor metabolizers. However, nearly 20% of the cohort could not be classified due to the presence of the *71 allele or other novel alleles.

The study highlights the need for further investigation into the functional impact of the *71 allele and emphasizes the importance of including diverse populations in pharmacogenomic research to ensure equitable healthcare.