TY - JOUR
T1 - Prevalence of CYP2C19 variant alleles and pharmacodynamic variability of aspirin and clopidogrel in Native Americans
AU - Oestreich, Julie H.
AU - Best, Lyle G.
AU - Dobesh, Paul P.
N1 - Funding Information:
This study was supported in part by grants from the American Association of Colleges of Pharmacy and the Cardiology Practice and Research Network of the American College of Clinical Pharmacy. The authors are solely responsible for the design of this study, all study analyses, the drafting of the manuscript, and its final contents.
PY - 2014/3
Y1 - 2014/3
N2 - Background The prevalence of variant alleles of the CYP2C19 gene has been determined for most population groups, but not Native Americans. Furthermore, the overall effectiveness of clopidogrel and aspirin has not been well studied in Native Americans, although this group has high mortality rates for cardiovascular disease and diabetes. Methods We recruited 50 volunteers from the Oglala Sioux Tribe with coronary artery disease taking aspirin and clopidogrel. Whole blood was collected for analysis using the VerifyNow P2Y12 and aspirin tests. Samples from the coronary artery disease patients and 50 additional tribal volunteers (n = 100 total) were genotyped for CYP2C19 variants*2,*3, and*17. Results The allele frequencies for CYP2C19*2 and CYP2C19*17 in the population group were 11% (95% CI 7%-16%) and 9% (95% CI 5%-13%), respectively. No subjects carried the CYP2C19*3 allele. The median PRU (P2Y12 reaction units) in the population group was 194 with wide variability (range 29-400). There was no significant effect of genotype on platelet aggregation as measured by the VerifyNow P2Y12 test (P =.77). The median ARU (aspirin reaction units) for the group was 437 (range 350-659), and 73% had aspirin reaction unit values <550. Conclusions The prevalence of variant CYP2C19 alleles is low in Native Americans of the Oglala Sioux Tribe compared with certain HapMap populations. The variable response to aspirin and clopidogrel in the Oglala Sioux Tribe is consistent with reported values for other groups as measured by the VerifyNow assay (Accumetrics, San Diego, CA).
AB - Background The prevalence of variant alleles of the CYP2C19 gene has been determined for most population groups, but not Native Americans. Furthermore, the overall effectiveness of clopidogrel and aspirin has not been well studied in Native Americans, although this group has high mortality rates for cardiovascular disease and diabetes. Methods We recruited 50 volunteers from the Oglala Sioux Tribe with coronary artery disease taking aspirin and clopidogrel. Whole blood was collected for analysis using the VerifyNow P2Y12 and aspirin tests. Samples from the coronary artery disease patients and 50 additional tribal volunteers (n = 100 total) were genotyped for CYP2C19 variants*2,*3, and*17. Results The allele frequencies for CYP2C19*2 and CYP2C19*17 in the population group were 11% (95% CI 7%-16%) and 9% (95% CI 5%-13%), respectively. No subjects carried the CYP2C19*3 allele. The median PRU (P2Y12 reaction units) in the population group was 194 with wide variability (range 29-400). There was no significant effect of genotype on platelet aggregation as measured by the VerifyNow P2Y12 test (P =.77). The median ARU (aspirin reaction units) for the group was 437 (range 350-659), and 73% had aspirin reaction unit values <550. Conclusions The prevalence of variant CYP2C19 alleles is low in Native Americans of the Oglala Sioux Tribe compared with certain HapMap populations. The variable response to aspirin and clopidogrel in the Oglala Sioux Tribe is consistent with reported values for other groups as measured by the VerifyNow assay (Accumetrics, San Diego, CA).
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U2 - 10.1016/j.ahj.2013.10.028
DO - 10.1016/j.ahj.2013.10.028
M3 - Article
C2 - 24576527
AN - SCOPUS:84896836743
VL - 167
SP - 413
EP - 418
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 3
ER -