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Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway Analyses for Platelet Reactivity and Clinical Outcomes of Repeat Revascularization After First PCI in Chinese Patients

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Abstract

Purpose

Major disadvantages of the percutaneous coronary intervention (PCI) are the high occurrence of repeat revascularization due to restenosis and disease progression. The current study aimed to identify indicators that can predict the risk of repeat revascularization.

Methods

A total of 143 patients who underwent PCI and had genetic test results were enrolled. We retrospectively reviewed their medical records after the first PCI. P2Y12 reaction unit (PRU) test results were obtained by VerifyNow; 4 candidate genes (NOS3, MMP3, AGT, and AGT1R) and 380 genes related to platelet activation-related processes and clopidogrel activity were selected for analysis. Repeat revascularization and in-stent restenosis (ISR) were used as clinical outcomes, and PRU and ADP aggregation rates were used as platelet function outcomes in analysis.

Results

After the first PCI, the incidence of repeat revascularization at 18, 30, and 42 months was 14.1% (20/142), 17.5% (24/137), and 39.7% (31/78), respectively. In the candidate gene analysis, rs7830 (NOS3) was associated with both ADP aggregation rate and 18- and 30-month ISR, and rs 62,275,847 (AGTR1) was associated with both ADP aggregation rate and 30-month ISR. In the pathway, gene-set analysis, the linkage rs471683 and rs7785386 of GNAI1|GNAT3 were associated with PRU and ADP aggregation rate, 18-month and 30-month ISR, and repeat revascularization within 30 months. Rs1715389 of GNAI1|GNAT3 was associated with both PRU and ADP aggregation rate, 18-month and 30-month ISR, and repeat revascularization within 30 months. Rs7313458 of ITPR2 was associated with PRU and ADP aggregation rate, 18-month and 30-month ISR, and repeat revascularization within 18 months.

Conclusions

The genetic polymorphisms of rs7830 (NOS3), rs62275874 (AGTR1), linkage rs471683 and rs7785386 (GNAI1|GNAT3), rs1715389 (GNAI1|GNAT3), and rs7313458 (ITPR2) may lead to an increased risk of in-stent restenosis and revascularization after the first PCI in Chinese patients by affecting the efficacy of clopidogrel. The above six SNP may be used as potential genetic biomarkers for high risk of in-stent restenosis and revascularization after the first PCI in Chinese patients.

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Data Availability

Availability of data and material has been described in the manuscript. Data would be provided upon request from the authors and in accordance with local regulations.

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Acknowledgements

We thank all study subjects and investigators for their participation in this study.

Funding

This study was supported by grants from the National Natural Science Foundation (No. 81872940, No. 81973395, and No. 82073935) of China and National Science and Technology Major Project for “Major New Drugs Innovation and Development” of China (No. 2017zx09101001).

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Authors and Affiliations

Authors

Contributions

Designed the research: Yimin Cui, Yanjun Gong, and Qian Xiang.

Enrolled patients: Yanjun Gong, Shuang Zhou, and Zining Wang.

Tested blood sample: Zhe Wang, Zhiyan Liu, Guangyan Mu, and Shuang Zhou.

Data acquisition: Shuang Zhou, Zhiyan Liu, and Qiufen Xie.

Analyzed data: Shuang Zhou, Zhe Wang, Zhiyan Liu, and Guangyan Mu.

Wrote the manuscript: Shuang Zhou, Zhe Wang, and Qian Xiang.

Corresponding authors

Correspondence to Qian Xiang, Yanjun Gong or Yimin Cui.

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All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Written informed consent was obtained from all study participants.

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The authors declare no competing interest.

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All participants provided written informed consent before enrollment in this study.

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Cite this article

Zhou, S., Wang, Z., Liu, Z. et al. Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway Analyses for Platelet Reactivity and Clinical Outcomes of Repeat Revascularization After First PCI in Chinese Patients. Cardiovasc Drugs Ther 37, 507–518 (2023). https://doi.org/10.1007/s10557-021-07281-0

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