The frequency of major ABCG2, SLCO1B1 and CYP2C9 variants in Asian, Native Hawaiian and Pacific Islander women subgroups: implications for personalized statins dosing

Author:

Alrajeh Khalifa12ORCID,AlAzzeh Ola1,Roman Youssef1ORCID

Affiliation:

1. Department of Pharmacotherapy & Outcome Science, Virginia Commonwealth University School of Pharmacy, 410 N 12th Street, Richmond, VA 23298, USA

2. Department of Pharmacy Practice, King Faisal University College of Clinical Pharmacy, PO Box 400, Hofuf, Eastern Province, 31982, Saudi Arabia

Abstract

Aim: The frequencies of SLCO1B1*5 and CYP2C9*2 and *3 in specific Asian, Native Hawaiian and Pacific Islander (NHPI) subgroups are unknown. Patients & methods: Repository DNA samples from 1064 women self-identifying as Filipino, Korean, Japanese, Native Hawaiian, Marshallese or Samoan and aged 18 years or older were used for targeted sequencing of three genetic variants (rs4149056, rs1799853 and rs1057910). Results: SLCO1B1*5 was significantly less frequent in NHPI women (0.5–6%) than in Europeans (16%). Except for Koreans, CYP2C9*2 (0–1.4%) and *3 (0.5–3%) were significantly less frequent in all subgroups than in Europeans (8 and 12.7%, respectively). Prior reports showed that Asian and NHPI individuals have significantly higher ABCG2 Q141K allele frequency (13–46%) than Europeans (9.4%). Combined phenotype rates for rosuvastatin and fluvastatin revealed that Filipinos and Koreans had the highest frequencies of statin-associated myopathy symptoms risk alleles. Conclusion: Differences in ABCG2, SLCO1B1 and CYP2C9 allele frequencies among different racial and ethnic subgroups highlight the need for increased diversity in pharmacogenetic research. Risk alleles for statin-associated myopathy symptoms are more prevalent in Filipinos, underscoring the importance of genotype-based statin dosing.

Funder

National Institute General Medical Sciences

the National Institute on Minority Health and Health Disparities

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Reference65 articles.

1. National Heart, Lung, and Blood Institute. GO Exome Sequencing Project (ESP). https://evs.gs.washington.edu/EVS/

2. Clinical Pharmacogenetics Implementation Consortium. CPIC® guideline for statins and SLCO1B1, ABCG2, and CYP2C9. (2022). https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

3. An Evidence‐Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine

4. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 , ABCG2 , and CYP2C9 genotypes and Statin‐Associated Musculoskeletal Symptoms

5. The United States 2020 Census data: implications for precision medicine and the research landscape

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