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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

General Research Article

Key Mutant Genes and Biological Pathways Involved in Aspirin Resistance in the Residents of the Chinese Plateau Area

Author(s): Jinchun Wu*, Rong Chang* and Yanmin Liu

Volume 27, Issue 4, 2024

Published on: 11 May, 2023

Page: [632 - 640] Pages: 9

DOI: 10.2174/1386207326666230418113637

Price: $65

Abstract

Introduction: Aspirin is used to prevent and treat cardiovascular diseases; however, some patients develop aspirin resistance.

Aim: We aimed to explore the potential molecular mechanisms underlying aspirin resistance in people living in the Chinese plateau area.

Methods: In total, 91 participants receiving aspirin treatment from the Qinghai plateau area were divided into the aspirin resistance and aspirin sensitivity groups. Genotyping was performed using the Sequence MASSarray. Differentially mutated genes between the two groups were analyzed using MAfTools. The annotation of differentially mutated genes was conducted based on the Metascape database.

Results and Discussion: In total, 48 differential SNP and 22 differential InDel mutant genes between the aspirin resistance and aspirin sensitivity groups were screened using Fisher’s exact test (P < 0.05). After the χ2 test, a total of 21 SNP mutant genes, including ZFPL1 and TLR3, and 19 InDel mutant genes were found to be differentially expressed between the two groups (P < 0.05). Functional analysis revealed that these differential SNP mutations were mainly enriched in aspirin resistance pathways, such as the Wnt signaling pathway. Furthermore, these genes were related to many diseases, including various aspirin indications.

Conclusion: This study identified several genes and pathways that could be involved in arachidonic acid metabolic processes and aspirin resistance progression, which will provide a theoretical understanding of the molecular mechanism of aspirin resistance.

Graphical Abstract

[1]
Al-Sofiani, M.E.; Derenbecker, R.; Quartuccio, M.; Kalyani, R.R. Aspirin for primary prevention of cardiovascular disease in diabetes: A review of the evidence. Curr. Diab. Rep., 2019, 19(10), 107.
[http://dx.doi.org/10.1007/s11892-019-1206-6] [PMID: 31544224]
[2]
Nudy, M.; Cooper, J.; Ghahramani, M.; Ruzieh, M.; Mandrola, J.; Foy, A.J. Aspirin for primary atherosclerotic cardiovascular disease prevention as baseline risk increases: A meta-regression analysis. Am. J. Med., 2020, 133(9), 1056-1064.
[http://dx.doi.org/10.1016/j.amjmed.2020.04.028] [PMID: 32445718]
[3]
Rocca, B.; Patrono, C. Aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: A new perspective. Diabetes Res. Clin. Pract., 2020, 160, 108008.
[http://dx.doi.org/10.1016/j.diabres.2020.108008] [PMID: 31926190]
[4]
Wiśniewski, A.; Sikora, J.; Sławińska, A.; Filipska, K.; Karczmarska-Wódzka, A.; Serafin, Z.; Kozera, G. High on-treatment platelet reactivity affects the extent of ischemic lesions in stroke patients due to large-vessel disease. J. Clin. Med., 2020, 9(1), 251.
[http://dx.doi.org/10.3390/jcm9010251] [PMID: 31963511]
[5]
Khodadi, E. Platelet function in cardiovascular disease: Activation of molecules and activation by molecules. Cardiovasc. Toxicol., 2020, 20(1), 1-10.
[http://dx.doi.org/10.1007/s12012-019-09555-4] [PMID: 31784932]
[6]
Barbarawi, M.; Kheiri, B.; Zayed, Y.; Gakhal, I.; Al-Abdouh, A.; Barbarawi, O.; Rashdan, L.; Rizk, F.; Bachuwa, G.; Alkotob, M.L. Aspirin efficacy in primary prevention: A meta-analysis of randomized controlled trials. High Blood Press. Cardiovasc. Prev., 2019, 26(4), 283-291.
[http://dx.doi.org/10.1007/s40292-019-00325-5] [PMID: 31280451]
[7]
Wang, J.; Liu, J.; Zhou, Y.; Wang, F.; Xu, K.; Kong, D.; Bai, J.; Chen, J.; Gong, X.; Meng, H.; Li, C. Association among PlA1/A2 gene polymorphism, laboratory aspirin resistance and clinical outcomes in patients with coronary artery disease: An updated meta-analysis. Sci. Rep., 2019, 9(1), 13177.
[http://dx.doi.org/10.1038/s41598-019-49123-y] [PMID: 31511539]
[8]
Taco-Vasquez, E.D.; Barrera, F.; Serrano-Duenas, M.; Jimenez, E.; Rocuts, A.; Riveros Perez, E. Association between blood viscosity and cardiovascular risk factors in patients with arterial hypertension in a high altitude setting. Cureus, 2019, 11(1), e3925.
[http://dx.doi.org/10.7759/cureus.3925] [PMID: 30937231]
[9]
Sun, Y.; Zhang, J.; Zhao, A.; Li, W.; Feng, Q.; Wang, R. Effects of intestinal flora on the pharmacokinetics and pharmacodynamics of aspirin in high-altitude hypoxia. PLoS One, 2020, 15(3), e0230197.
[http://dx.doi.org/10.1371/journal.pone.0230197] [PMID: 32163488]
[10]
McCullough, P.A.; Vasudevan, A.; Sathyamoorthy, M.; Schussler, J.M.; Velasco, C.E.; Lopez, L.R.; Swift, C.; Peterson, M.; Bennett-Firmin, J.; Schiffmann, R.; Bottiglieri, T. Urinary 11-dehydro-thromboxane B2 and mortality in patients with stable coronary artery disease. Am. J. Cardiol., 2017, 119(7), 972-977.
[http://dx.doi.org/10.1016/j.amjcard.2016.12.004] [PMID: 28139223]
[11]
Xu, T.; Hu, X.X.; Liu, X.X.; Wang, H.J.; Lin, K.; Pan, Y.Q.; Sun, H.L.; Peng, H.X.; Chen, X.X.; Wang, S.K.; He, B.S. Association between SNPs in long non-coding RNAs and the risk of female breast cancer in a Chinese population. J. Cancer, 2017, 8(7), 1162-1169.
[http://dx.doi.org/10.7150/jca.18055] [PMID: 28607590]
[12]
Fang, B.; Li, Y.; Chen, C.; Wei, Q.; Zheng, J.; Liu, Y.; He, W.; Lin, D.; Li, G.; Hou, Y.; Xu, L. Huo Xue Tong Luo capsule ameliorates osteonecrosis of femoral head through inhibiting lncRNA-Miat. J. Ethnopharmacol., 2019, 238, 111862.
[http://dx.doi.org/10.1016/j.jep.2019.111862] [PMID: 30970282]
[13]
Liu, L.; Huang, J.; Wei, B.; Mo, J.; Wei, Q.; Chen, C.; Yan, W.; Huang, X.; He, F.; Qin, L.; Huang, H.; Li, X.; Pan, X. Multiomics analysis of genetics and epigenetics reveals pathogenesis and therapeutic targets for atrial fibrillation. BioMed Res. Int., 2021, 2021, 1-36.
[http://dx.doi.org/10.1155/2021/6644827] [PMID: 33834070]
[14]
Odumpatta, R.; Mohanapriya, A. Next generation sequencing exome data analysis aids in the discovery of SNP and INDEL patterns in Parkinson’s disease. Genomics, 2020, 112(5), 3722-3728.
[http://dx.doi.org/10.1016/j.ygeno.2020.04.025] [PMID: 32348865]
[15]
Zhou, Y.; Zhou, B.; Pache, L.; Chang, M.; Khodabakhshi, A.H.; Tanaseichuk, O.; Benner, C.; Chanda, S.K. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun., 2019, 10(1), 1523.
[http://dx.doi.org/10.1038/s41467-019-09234-6] [PMID: 30944313]
[16]
Yi, X; Zhou, Q; Lin, J; Chi, L; Han, Z Platelet response to aspirin in Chinese stroke patients is independent of genetic polymorphisms of COX-1 C50T and COX-2 G765C. J. Atheroscler. Thromb., 2013, 20(1), 65-72.
[http://dx.doi.org/10.5551/jat.14092] [PMID: 22972377]
[17]
Fong, J.; Cheng-Ching, E.; Hussain, M.S.; Katzan, I.; Gupta, R. Predictors of biochemical aspirin and clopidogrel resistance in patients with ischemic stroke. J. Stroke Cerebrovasc. Dis., 2011, 20(3), 227-230.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2009.12.004] [PMID: 20621513]
[18]
Xie, Y.Z.; Ma, W.L.; Meng, J.M.; Ren, X.Q. Knockdown of ZFPL1 results in increased autophagy and autophagy-related cell death in NCI-N87 and BGC-823 human gastric carcinoma cell lines. Mol. Med. Rep., 2017, 15(5), 2633-2642.
[http://dx.doi.org/10.3892/mmr.2017.6300] [PMID: 28447717]
[19]
Chen, J.; Wang, L.; Liu, W.H.; Shi, J.; Zhong, Y.; Liu, S.J.; Liu, S.M. Aspirin protects human coronary artery endothelial cells by inducing autophagy. Physiol. Int., 2020, 107(2), 294-305.
[http://dx.doi.org/10.1556/2060.2020.00029] [PMID: 32750030]
[20]
Ranjith-Kumar, C.T.; Miller, W.; Sun, J.; Xiong, J.; Santos, J.; Yarbrough, I.; Lamb, R.J.; Mills, J.; Duffy, K.E.; Hoose, S.; Cunningham, M.; Holzenburg, A.; Mbow, M.L.; Sarisky, R.T.; Kao, C.C. Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and expression in cultured cells. J. Biol. Chem., 2007, 282(24), 17696-17705.
[http://dx.doi.org/10.1074/jbc.M700209200] [PMID: 17434873]
[21]
Månsson, A.; Fransson, M.; Adner, M.; Benson, M.; Uddman, R.; Björnsson, S.; Cardell, L.O. TLR3 in human eosinophils: Functional effects and decreased expression during allergic rhinitis. Int. Arch. Allergy Immunol., 2010, 151(2), 118-128.
[http://dx.doi.org/10.1159/000236001] [PMID: 19752565]
[22]
Palikhe, N.S.; Kim, S.H.; Kim, J.H.; Losol, P.; Ye, Y.M.; Park, H.S. Role of toll-like receptor 3 variants in aspirin-exacerbated respiratory disease. Allergy Asthma Immunol. Res., 2011, 3(2), 123-127.
[http://dx.doi.org/10.4168/aair.2011.3.2.123] [PMID: 21461252]
[23]
Ruipérez, V.; Astudillo, A.M.; Balboa, M.A. Balsinde, J Coordinate regulation of TLR-mediated arachidonic acid mobilization in macrophages by group IVA and group V phospholipase A2s. J. Immunol., 2009, 182(6), 3877-3883.
[24]
Salvi, V.; Vaira, X.; Gianello, V.; Vermi, W.; Bugatti, M.; Sozzani, S.; Bosisio, D. TLR signalling pathways diverge in their ability to induce PGE 2. Mediators Inflamm., 2016, 2016, 1-10.
[http://dx.doi.org/10.1155/2016/5678046] [PMID: 27630451]
[25]
Pindado, J.; Balsinde, J.; Balboa, M.A. TLR3-dependent induction of nitric oxide synthase in RAW 264.7 macrophage-like cells via a cytosolic phospholipase A2/cyclooxygenase-2 pathway. J. Immunol., 2007, 179(7), 4821-4828.
[26]
Khan, P.; Bhattacharya, A.; Sengupta, D.; Banerjee, S.; Adhikary, A.; Das, T. Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration. Sci. Rep., 2019, 9(1), 16913.
[http://dx.doi.org/10.1038/s41598-019-53134-0] [PMID: 31729456]
[27]
Jiang, W.; Yan, Y.; Chen, M.; Luo, G.; Hao, J.; Pan, J.; Hu, S.; Guo, P.; Li, W.; Wang, R.; Zuo, Y.; Sun, Y.; Sui, S.; Yu, W.; Pan, Z.; Zou, K.; Zheng, Z.; Deng, W.; Wu, X.; Guo, W. Aspirin enhances the sensitivity of colon cancer cells to cisplatin by abrogating the binding of NF-κB to the COX-2 promoter. Aging, 2020, 12(1), 611-627.
[http://dx.doi.org/10.18632/aging.102644] [PMID: 31905343]
[28]
Zhang, X.; Chen, B.; Wu, J.; Sha, J.; Yang, B.; Zhu, J.; Sun, J.; Hartung, J.; Bao, E. Aspirin enhances the protection of Hsp90 from heat-stressed injury in cardiac microvascular endothelial cells through PI3K-Akt and PKM2 pathways. Cells, 2020, 9(1), 243.
[http://dx.doi.org/10.3390/cells9010243] [PMID: 31963688]
[29]
Cheng, P.; Liao, H.Y.; Zhang, H.H. The role of Wnt/mTOR signaling in spinal cord injury. J. Clin. Orthop. Trauma, 2022, 25, 101760.
[http://dx.doi.org/10.1016/j.jcot.2022.101760] [PMID: 35070684]
[30]
Lee, S.H.; Kim, M.H.; Han, H.J. Arachidonic acid potentiates hypoxia-induced VEGF expression in mouse embryonic stem cells: involvement of Notch, Wnt, and HIF-1α. Am. J. Physiol. Cell Physiol., 2009, 297(1), C207-C216.
[http://dx.doi.org/10.1152/ajpcell.00579.2008] [PMID: 19339510]
[31]
Apte, R.S.; Chen, D.S.; Ferrara, N. VEGF in signaling and disease: Beyond discovery and development. Cell, 2019, 176(6), 1248-1264.
[http://dx.doi.org/10.1016/j.cell.2019.01.021] [PMID: 30849371]
[32]
Li, L.; Wang, H.; Liu, H.; Liu, Z.; Li, L.; Ding, K.; Wang, G.; Song, J.; Fu, R. Gene mutations associated with thrombosis detected by whole‐exome sequencing in paroxysmal nocturnal hemoglobinuria. Int. J. Lab. Hematol., 2019, 41(3), 424-432.
[http://dx.doi.org/10.1111/ijlh.13018] [PMID: 30970179]

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