MirSNPs in clopidogrel metabolism genes predict cardiovascular disease risk: a case-control study and meta-analysis

Pharmacogenomics. 2021 Jan;22(2):99-113. doi: 10.2217/pgs-2020-0110. Epub 2020 Dec 24.

Abstract

Aim: The present study was conducted to decipher the inter-relationship of SNPs and miRNAs involved in pharmacogenomics of clopidogrel on predisposition to cardiovascular diseases (CVDs). Materials & methods: A case-control study was conducted on 410 cases and 386 controls to analyze the association of 13 mirSNPs on CVDs risk. Genotyping was performed by tetra-primer amplification refractory mutation system PCR and validated using Sanger DNA sequencing. miRNA expression analysis was performed using TaqMan assays. A meta-analysis was performed for PON1 rs662 with coronary artery disease. Results & conclusion:PON1 rs662, PON1 rs3917577, CYP3A5 rs15524, COL4A1 rs874204 and PTGIR rs1126510 polymorphisms showed association with CVDs. The miRNA hsa-miR-224-5p showed differential expression in the PON1 rs3917577 GG genotype. The meta-analysis showed the population-specific impact of PON1 rs662 on South Asian and Middle East populations.

Keywords: PON1; cardiovascular diseases; meta-analysis; miRNAs; mirSNPs.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aryldialkylphosphatase / genetics
  • Asian People
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / genetics*
  • Case-Control Studies
  • Clopidogrel / pharmacokinetics*
  • Collagen Type IV / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Middle East
  • Mutation
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • COL4A1 protein, human
  • Collagen Type IV
  • MIRN224 microRNA, human
  • MicroRNAs
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Aryldialkylphosphatase
  • PON1 protein, human