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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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:37

Enthalten in:

Cardiovascular drugs and therapy - 37(2023), 3 vom: 03. Juni, Seite 507-518

Sprache:

Englisch

Beteiligte Personen:

Zhou, Shuang [VerfasserIn]
Wang, Zhe [VerfasserIn]
Liu, Zhiyan [VerfasserIn]
Mu, Guangyan [VerfasserIn]
Xie, Qiufen [VerfasserIn]
Wang, Zining [VerfasserIn]
Xiang, Qian [VerfasserIn]
Gong, Yanjun [VerfasserIn]
Cui, Yimin [VerfasserIn]

Links:

Volltext

Themen:

A74586SNO7
Clopidogrel
EC 1.14.13.39
EC 3.4.24.17
Genetic polymorphism
In-stent restenosis
Journal Article
MMP3 protein, human
Matrix Metalloproteinase 3
NOS3 protein, human
Nitric Oxide Synthase Type III
Percutaneous coronary intervention
Platelet Aggregation Inhibitors
Repeat revascularization

Anmerkungen:

Date Completed 22.05.2023

Date Revised 22.05.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s10557-021-07281-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM333971248