Allelic diversity of the pharmacogenes CYP2D6 and CYP2C19 in Māori from Te Tairāwhiti, Aotearoa New Zealand

CYP2C19 and CYP2D6 are two important pharmacogenes responsible for metabolising a wide range of medications. Both genes exhibit a high level of variation, which can lead to variable activity of the enzymes they encode, with risks of adverse drug reactions and treatment failure. Understanding this variation is therefore of great importance, but the full extent of variability in these genes is not yet documented, particularly for understudied populations. We employed targeted nanopore sequencing to identify genetic variants within CYP2C19 and CYP2D6 for a group of Māori individuals, largely affiliated with the Ngāti Porou iwi from Te Tairāwhiti (Gisborne), Aotearoa New Zealand. 135 CYP2D6 and 73 CYP2C19 genotypes were sequenced, with metaboliser phenotypes inferred for the majority of participants. CYP2D6 normal metabolisers make up 54% of the cohort and 45% of the cohort are CYP2C19 intermediate metabolisers. Nearly 20% had an uncertain CYP2D6 activity due to the prevalence of CYP2D6*71, which is of unknown functional impact. Understanding the extent of variation in these genes should contribute to equitable application of pharmacogenetic testing in Aotearoa New Zealand.