Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel

J Clin Lab Anal. 2021 Apr;35(4):e23713. doi: 10.1002/jcla.23713. Epub 2021 Jan 26.

Abstract

Background: Changes in circadian rhythm are related to various diseases, such as immune system diseases and cardiovascular diseases. The PERIOD3 (PER3) clock gene is one of the most important genes in the rhythm regulation system. Our goal was to evaluate the possible association between the PER3 rs228729 (T/C) polymorphism or PER3 rs2797685(T/C) polymorphism and clopidogrel resistance (CR) and to study the impact of clinical baseline data on clopidogrel resistance.

Methods: PER3 polymorphisms rs2797685 (T/C) and rs228729 (T/C) were assessed in 156 patients with (72) and without (84) CR. Blood samples were collected and analyzed after the application of clopidogrel for interventional therapy.

Results: Age, albumin, PLT, and PCT levels influenced the risk of CR (p < 0.05). For rs2797685, when the PCT value was greater than 0.19, patients with the TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (PCT ≥ 0.19, p = 0.014; PCT p = 0.004). In patients with albumin values greater than 40 or PCT greater than 0.19, those with the rs228729 TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (albumin≥40, TT+TC:CC, p = 0.01, albumin p = 0.005; PCT ≥ 0.19, TT+TC:CC, p < 0.001, PCT p = 0.004). Logistic regression analysis of clinical baseline data and genotype showed that high albumin is a protective factor against clopidogrel resistance. The PER3 gene polymorphism has no clear correlation with clopidogrel resistance.

Conclusion: In summary, our research shows that PER3 SNPs may be helpful to assess the pathogenesis of CR.

Keywords: PERIOD3; acute coronary syndrome; clopidogrel resistance; percutaneous coronary interventions; single-nucleotide polymorphisms.

MeSH terms

  • Aged
  • Asian People / genetics*
  • Blood Platelets / metabolism
  • Case-Control Studies
  • Clopidogrel / pharmacology*
  • Drug Resistance / drug effects
  • Drug Resistance / genetics*
  • Ethnicity / genetics*
  • Female
  • Genetic Association Studies*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Period Circadian Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • PER3 protein, human
  • Period Circadian Proteins
  • Clopidogrel