Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel
Nan Zheng1, Fengying Yin2, Qinglin Yu3
1Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, P.R. China.
Insights
The PERIOD3 (PER3) gene
Area of Science:
- Genetics
- Pharmacogenomics
- Chronobiology
Background:
- Circadian rhythm disruptions are linked to various diseases, including immune and cardiovascular conditions.
- The PERIOD3 (PER3) clock gene plays a crucial role in regulating biological rhythms.
- Clopidogrel resistance (CR) is a significant clinical concern impacting treatment efficacy.
Purpose of the Study:
- To investigate the association between PER3 gene polymorphisms (rs228729 and rs2797685) and clopidogrel resistance (CR).
- To determine the influence of clinical baseline data on the risk of developing clopidogrel resistance.
Main Methods:
- Genotyping of PER3 polymorphisms rs2797685 (T/C) and rs228729 (T/C) in 156 patients.
- Patients were categorized based on the presence (72) or absence (84) of clopidogrel resistance.
- Blood samples were analyzed post-clopidogrel administration for interventional therapy.
Main Results:
- Age, albumin, platelet count (PLT), and plateletcrit (PCT) levels significantly influenced CR risk.
- For rs2797685, PCT levels ≥ 0.19 were associated with increased CR risk in TT+TC genotypes compared to CC.
- For rs228729, elevated albumin (≥40) or PCT (≥0.19) correlated with higher CR risk in TT+TC genotypes.
- Logistic regression identified high albumin as a protective factor against clopidogrel resistance.
- No clear correlation was found between PER3 gene polymorphism and clopidogrel resistance.
Conclusions:
- PER3 single nucleotide polymorphisms (SNPs) may contribute to understanding the pathogenesis of clopidogrel resistance.
- Clinical factors like albumin and PCT levels are important predictors of clopidogrel resistance.
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.
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