Genetic determinants of dabigatran safety (CES1 gene rs2244613 polymorphism) in the Russian population: multi-ethnic analysis

Mol Biol Rep. 2019 Jun;46(3):2761-2769. doi: 10.1007/s11033-019-04722-w. Epub 2019 Mar 8.

Abstract

This study was aimed to investigate the prevalence of the CES1 gene (c.1168-33A > C, rs2244613) polymorphism among 12 different ethnic groups living in Russia to provide a basis for future clinical studies concerning genetic determinants of dabigatran safety. The study involved 1630 apparently healthy, unrelated, and chronic medication-free volunteers of both genders from 12 different ethnic groups in Russia: 136 Russians, 90 Avars, 50 Dargins, 46 Laks, 120 Kabardians, 112 Balkars, 244 Ossetians, 206 Mari, 204 Mordvinians, 238 Chuvashes, 114 Buryats and 70 Nanays. Genotyping was performed by using real-time polymerase chain reaction-based methods. The allelic prevalence of the ethnic groups was compared with Caucasus population participating in the RE-LY study. Statistically significant differences for the following gene polymorphism were found between all ethnic groups and RE-LY participants. Based on obtained results, it can be assumed that patients of all ethnic groups living in Russia taking dabigatran have a lower risk of bleeding.

Keywords: CES1; Dabigatran; Ethnicity; Pharmacogenetics; Rs2244613.

MeSH terms

  • Alleles
  • Biomarkers, Pharmacological / blood
  • Carboxylic Ester Hydrolases / genetics*
  • Carboxylic Ester Hydrolases / metabolism
  • Dabigatran / pharmacology
  • Dabigatran / therapeutic use
  • Ethnicity / genetics
  • Female
  • Gene Frequency / genetics
  • Genetics, Population
  • Genotype
  • Healthy Volunteers
  • Humans
  • Male
  • Pharmacogenetics / methods
  • Polymorphism, Single Nucleotide / genetics
  • Prospective Studies
  • Russia
  • White People / genetics

Substances

  • Biomarkers, Pharmacological
  • Carboxylic Ester Hydrolases
  • CES1 protein, human
  • Dabigatran