Abstract 194: Differential Prevalence of Loss/Gain of Function Alleles Affecting Response to Clopidogrel in the Hmong Underscores the Importance of Genotyping Unique Subpopulations as a Means to Address Existing Health Disparities

Abstract

Introduction: Standard of care for Acute Coronary Syndromes (ACS) includes dual antiplatelet therapy (e.g. aspirin and clopidogrel). CYP2C19 loss of function (*2, *3) or gain of function (*17) alleles are associated with clopidogrel’s bioactivation, antiplatelet effectiveness and clinical outcomes leading to the development of Clinical Pharmacogenomic Implementation Consortium (CPIC) guidelines. Currently the prevalence of CYP2C19 variants in the Hmong - a unique Asian population numbering over 60,000 in Minnesota - is unknown. Given that they are experiencing a surge in CVD, including ACS, we sought to compare their Minor Allele Frequencies (MAFs) for CYP2C19 *2, *3, and *17 with White Non-Hispanic and Han-Chinese. We evaluated the prevalence of *2 (rs4244285) or *3 (rs4986893), or *17 (rs12248560) alleles between the Hmong and those observed in 1) White Non-Hispanics and 2) Han-Chinese. To achieve this, DNA from Hmong was genotyped for the relevant Single Nucleotide Polymorphisms (SNPs) and compared to published (PMID: 21716271) MAFs for White Non-Hispanic and Han-Chinese cohorts Methods: Salivary DNA from 235 Hmong residing in either Minnesota or Wisconsin was genotyped for relevant SNPs by Sequenom iPlex Gold assay. MAFs between groups were compared by Chi-Square or Fisher’s exact test. A Bonferroni corrected significance level of 0.017 was considered statistically significant. Results: Hmong MAFs were higher for *2 (37%, p=0.0001) but lower for *17 (0.2%, p=0.0001) compared to the White Non-Hispanic cohort (13% and 23% respectively). Hmong MAFs were higher for *2 (37%, p=0.0001) but lower for *3 (0.2%, p=0.0001) compared to the Han-Chinese cohort (25% and 3%, respectively). Conclusions: Hmong have a higher prevalence of the loss of function allele, *2, compared to both reference cohorts. Hmong also have significantly different MAFs for both loss of function alleles, *2 and *3, compared to the Han-Chinese cohort. Both conclusions suggest that drug selection cannot be guided by race alone. Our data further underscores the importance of genotyping unique sub-populations as a means to mitigate existing health disparities in the availability of data which facilitate optimal drug selection.