Prevalence of pharmacogenomic variants affecting the efficacy of clopidogrel therapy in the Hispanic Community Health Study/Study of Latinos cohort

Pharmacogenomics. 2019 Jan;20(2):75-83. doi: 10.2217/pgs-2018-0148. Epub 2018 Dec 6.

Abstract

Purpose: Although clopidogrel is the most widely used oral P2Y12 receptor antagonist, up to 10% of acute coronary syndrome patients treated with clopidogrel will experience a recurrent myocardial infarction and 2-3% will experience stent thrombosis within 1 year. The purpose of this research is to describe the prevalence of pharmacogene variants associated with clopidogrel responsiveness (CYP2C19, B4GALT2, ABCB1, PON1, CES1 and P2RY12) in Hispanic/Latino patients of diverse backgrounds.

Methods: Minor allele frequencies of nine variants from participants of Hispanic Community Health Study/Study of Latinos were compared between subpopulations as well as to continental ancestry references using z-test for independent proportions.

Results: MAFs for six out of nine variants differed between Caribbean and Mainland subpopulations (p < 0.05). Compared with European reference group, MAFs of ABCB1, CES1 and PON1 were higher in Hispanic Community Health Study/Study of Latinos, whereas B4GALT2 and CYP2C19*2 and *17 were lower.

Conclusion: Significant differences in the prevalence of most pharmacogenomic variants related to clopidogrel response provide a foundation to better inform ongoing and future clinical studies of clopidogrel pharmacogenetics in the US Hispanic/Latino populations.

Keywords: Hispanic; Latino; clopidogrel; pharmacogenes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / genetics
  • Aged
  • Aryldialkylphosphatase / genetics
  • Carboxylic Ester Hydrolases / genetics
  • Clopidogrel / adverse effects*
  • Clopidogrel / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics
  • Female
  • Galactosyltransferases / genetics
  • Gene Frequency / genetics
  • Genotype
  • Hispanic or Latino / genetics
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / pathology
  • Pharmacogenomic Variants
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymorphism, Single Nucleotide / genetics
  • Stents
  • Thrombosis / chemically induced
  • Thrombosis / genetics*
  • Thrombosis / pathology

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • B4GALT2 protein, human
  • Galactosyltransferases
  • Carboxylic Ester Hydrolases
  • CES1 protein, human
  • Aryldialkylphosphatase
  • PON1 protein, human