Aim: Prevalence of clinically actionable genetic variants of CYP2C19 is lacking in specific population subgroups. This study aims to assess the frequencies of CYP2C19*2, *3, and *17 in Asian, Native Hawaiian and Pacific Islander (NHPI) population subgroups compared with Europeans. Patients & methods: The study included repository DNA samples of 1064 women, 18 years or older, who self-reported as Filipino, Korean, Japanese, Native Hawaiian, Marshallese and Samoan. Results: The overall frequencies of CYP2C19*2 (25-36%) and CYP2C19*3 (2.5-10%) were significantly higher in all our subgroups than in Europeans (15 and 0.02%, respectively). The overall frequency of CYP2C19*17 was significantly lower in all our subgroups (1-6%) than in Europeans (21.7%). Conclusion: This is the first report on the frequencies of CYP2C19*2, *3, and *17 in women of Asian and NHPI descent with distinct population subgroup differences. Differential allele frequencies of CYP2C19 among population subgroups underscore the importance of increasing racial and ethnic diversity in pharmacogenetic research.
Keywords: Asian subgroups; CYP450 enzymes; Hawaii clopidogrel lawsuit; Native Hawaiians; Pacific Islanders subgroups; genomics; health disparities; pharmacogenetics; race and ethnicity.
CYP2C19 encodes the CYP2C19 drug-metabolizing enzyme, a key protein in the liver involved in breaking down many commonly prescribed drugs. Individuals of Asian ancestry are more likely to have variations in this gene that could make it either less functional or non-functional. Racial categorization of Asian and Native Hawaiian and Pacific Islander (NHPI) groups is broad and overlooks possible genetic differences between the population subgroups. In this study, we used biobank DNA to examine the frequency of three genetic variants in CYP2C19 among 1064 Asian and NHPI women. We compared this group to a large multi-ethnic population including 2.2 million people. Our study provides the first report on CYP2C19 variants frequency among specific Asian and NHPI subgroups. Notably, Native Hawaiians have distinct variant frequencies compared with other Asian and Pacific Islander subgroups. Knowledge of the frequency of CYP2C19 gene variations in under-represented population subgroups is needed to advance personalized medicine and reduce racial health disparities in genetic research.