Association Between Paraoxonase 1 (PON 1) And Apolipoprotein E (APO E) Polymorphism with Lipid Profile in Acute Coronary Syndrome Patients

Authors: Yadasht Hayder1 & Mudhir Sabir Shekha2
1Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
2Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
2Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

Abstract: Objective: Acute coronary syndromes (ACS) are categorized by a sudden reduction in blood supply to the heart and include ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina. The aim of the present study is to evaluate whether the PON1 and APO E genes single nucleotide polymorphisms (SNPs) are associated with the presence of acute coronary syndrome (ACS) and lipid profiles in a case-control association study in an Iraqi Kurdistan population.
Methods: We genotyped two single nucleotide polymorphisms (SNPs) in APOE and PON 1 genes and compared patients who had an initial ACS with patients who presented with stable exertional angina.
Results: A total of 77 samples, including patients with ACS (N = 61), and those with chest pain syndrome (controls, N = 16) were enrolled. Genotyping for PON1 and APO E genes was performed using the PCR assay.
A series of statistical analyses were performed to investigate the association between PON1 and APO E genes SNPs and the susceptibility to ACS. The results revealed a non-significant association of APOE with ACS risk in which £2 (P = 0.585) which was found in all patients and control except 2 patients and 1 control that carried £3 (P = 0.508). £3 was the risk factor, PON 1 was non significantly associated with ACS in which the A allele (P=0.781) in which mostly found in ACS patients in comparison to the control group and it’s a strong risk factor for the disease. Also, T allele (P=0.127) found mostly in ACS patients in comparison to the control group. Logistic regression analyses further revealed an increased risk for ACS in A allele carrier, when compared to those with TT homozygotes (odds ratio: 1.199, 95% CI 0.420-3.756, P = 0.781). Furthermore, there were not any significant differences between lipids profile with both genes (APO E and PON 1).
The results of the present study suggested that the PON1 and APO E may play a role in the pathogenesis of Acute coronary syndrome in Kurdistan /Erbil population and that a decrease in PON1 activity may be a valuable marker for monitoring the development of the atherosclerosis process and the associated cardiovascular complications.

Keywords: PON 1 Gene, APO E Gene, Polymorphism, Lipid Profiles, Acute Coronary Syndrome Patients

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Doi: 10.23918/eajse.v9i1p340

Published: February 16, 2023

References

Amini, M., Zayeri, F., & Salehi, M. (2021). Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: results from global burden of disease study 2017. BMC Public Health, 21(1), 401. doi:10.1186/s12889-021-10429-0

Association, C. S. o. C. o. C. M., & zhi, E. B. o. C. J. o. C. J. Z. x. x. g. b. z. (2007). Guideline for diagnosis and treatment of patients with unstable angina and non-ST-segment elevation myocardial infarction. 35(4), 295-304.

Bergmark, B. A., Mathenge, N., Merlini, P. A., Lawrence-Wright, M. B., & Giugliano, R. P. (2022). Acute coronary syndromes. Lancet, 399(10332), 1347-1358. doi:10.1016/s0140-6736(21)02391-6

Bhatt, D. L., Lopes, R. D., & Harrington, R. A. (2022). Diagnosis and Treatment of Acute Coronary Syndromes: A Review. Jama, 327(7), 662-675. doi:10.1001/jama.2022.0358

Bounafaa, A., Berrougui, H., Ghalim, N., Nasser, B., Bagri, A., Moujahid, A., . . . Khalil, A. (2015). Association between Paraoxonase 1 (PON1) Polymorphisms and the Risk of Acute Coronary Syndrome in a North African Population. PLOS ONE, 10(8), e0133719. doi: 10.1371/journal.pone.0133719

Broce, I. J., Tan, C. H., Fan, C. C., Jansen, I., Savage, J. E., Witoelar, A., . . . Desikan, R. S. (2019). Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease. Acta Neuropathol, 137(2), 209-226. doi:10.1007/s00401-018-1928-6

Corbo, R. M., & Scacchi, R. (1999). Apolipoprotein E (APOE) allele distribution in the world. Is APOE* 4 a ‘thrifty’allele? Annals of human genetics, 63(4), 301-310.

Eichner, J. E., Dunn, S. T., Perveen, G., Thompson, D. M., Stewart, K. E., & Stroehla, B. C. (2002). Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol, 155(6), 487-495. doi:10.1093/aje/155.6.487

El Hadri, K., Smith, R., Duplus, E., & El Amri, C. (2021). Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target. Int J Mol Sci, 23(1). doi:10.3390/ijms23010077

Glanz, V., Bezsonov, E. E., Soldatov, V., & Orekhov, A. N. (2022). Thirty-Five-Year History of Desialylated Lipoproteins Discovered by Vladimir Tertov. Biomedicines, 10(5). doi:10.3390/biomedicines10051174

Hashemi, M., Moazeni-Roodi, A., Fazaeli, A., Sandoughi, M., Taheri, M., Bardestani, G., . . . Ghavami, S. (2010). The L 55 M polymorphism of paraoxonase-1 is a risk factor for rheumatoid arthritis. Genetics and Molecular Research, 9(3), 1735-1741.

Hou, J., Deng, Q., Guo, X., Deng, X., Zhong, W., & Zhong, Z. (2020). Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China. Lipids Health Dis, 19(1), 139. doi:10.1186/s12944-020-01323-6

Khatana, C., Saini, N. K., Chakrabarti, S., Saini, V., Sharma, A., Saini, R. V., & Saini, A. K. (2020). Mechanistic Insights into the Oxidized Low-Density Lipoprotein-Induced Atherosclerosis. Oxid Med Cell Longev, 2020, 5245308. doi:10.1155/2020/5245308

Lin, Y., Pan, W., Ning, S., Song, X., Jin, Z., & Lv, S. (2013). Prevalence and management of hypertension in patients with acute coronary syndrome vary with gender: Observations from the Chinese registry of acute coronary events (CRACE). Molecular Medicine Reports, 8(1), 173-177.

Mahrooz, A., Mackness, M., Bagheri, A., Ghaffari-Cherati, M., & Masoumi, P. (2019). The epigenetic regulation of paraoxonase 1 (PON1) as an important enzyme in HDL function: The missing link between environmental and genetic regulation. Clinical Biochemistry, 73, 1-10. doi:https://doi.org/10.1016/j.clinbiochem.2019.07.010

Members, A. T. F., Steg, P. G., James, S. K., Atar, D., Badano, L. P., Lundqvist, C. B., . . . Ducrocq, G. J. E. h. j. (2012). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). 33(20), 2569-2619.

Norhammar, A., Malmberg, K., Diderholm, E., Lagerqvist, B., Lindahl, B., Rydén, L., & Wallentin, L. (2004). Diabetes mellitus: the major risk factor in unstable coronary artery disease even after consideration of the extent of coronary artery disease and benefits of revascularization. J Am Coll Cardiol, 43(4), 585-591.

Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M., . . . Fuster, V. (2020). Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol, 76(25), 2982-3021. doi:10.1016/j.jacc.2020.11.010

Sachdeva, A., Cannon, C. P., Deedwania, P. C., LaBresh, K. A., Smith Jr, S. C., Dai, D., . . . Fonarow, G. C. (2009). Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. American heart journal, 157(1), 111-117. e112.

Shunmoogam, N., Naidoo, P., & Chilton, R. (2018). Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance. Vascular health and risk management, 14, 137.

Taler-Verčič, A., Goličnik, M., & Bavec, A. (2020). The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3. Molecules, 25(24). doi:10.3390/molecules25245980

Tréguier, Y., Bull-Maurer, A., & Roingeard, P. (2022). Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses. Int J Mol Sci, 23(7). doi:10.3390/ijms23073676

Vavlukis, M., Vavlukis, A., Krsteva, K., & Topuzovska, S. (2022). Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development. Front Genet, 13, 966413. doi:10.3389/fgene.2022.966413

Wu, J., Qiu, L., Guo, X.-z., Xu, T., Cheng, X.-q., Zhang, L., . . . Ni, L. (2014). Apolipoprotein E gene polymorphisms are associated with primary hyperuricemia in a Chinese population. PLoS One, 9(10), e110864.

Xu, C., Yu, B., Zhao, X., Lin, X., Tang, X., Liu, Z., . . . Li, L. (2022). Valosin Containing Protein as a Specific Biomarker for Predicting the Development of Acute Coronary Syndrome and Its Complication. Front Cardiovasc Med, 9, 803532. doi:10.3389/fcvm.2022.803532