Single Nucleotide Variation in the Promoter Region of the APOA1 Gene as a Candidate Biomarker for Dyslipidemia

Toeti Rahajoe; Kartika Nugraheni; Pinda Ayu Widiyani; Balqis Aureola Putri Asihanto; Aprilia Indra Kartika

doi:10.31965/infokes.Vol21.Iss4.1222

Authors

Toeti Rahajoe Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Universitas Muhammadiyah Semarang, Semarang, Central Java, Indonesia
Kartika Nugraheni Department of Nutrition, Faculty of Nursing and Health Science, Universitas Muhammadiyah Semarang, Semarang, Central Java, Indonesia
Pinda Ayu Widiyani Master of Public Health, Universitas Negeri Semarang, Semarang, Central Java, Indonesia
Balqis Aureola Putri Asihanto Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Universitas Muhammadiyah Semarang, Semarang, Central Java, Indonesia
Aprilia Indra Kartika Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Universitas Muhammadiyah Semarang, Semarang, Central Java, Indonesia

DOI:

https://doi.org/10.31965/infokes.Vol21.Iss4.1222

Keywords:

APOA-1gene, Dyslipidemia, Polymorphism

Abstract

Dyslipidemia is a lipid profile abnormality that can escalate the risk of cardiovascular disease. The rate of cardiovascular events in Indonesia is very high. One of the causes of dyslipidemia is due to polymorphisms in genes associated with lipid metabolism. The APOA-1 gene encodes the APOA-1 protein which functions to regulate HDL protein synthesis. The objective of this study is to determine APOA1 gene polymorphisms in patients with dyslipidemia. Samples of healthy controls and dyslipidemia patients were used in this investigation. The lipid profiles of the patients and normal controls are determined at the onset of the study. Following DNA extraction, the APOA-1 gene was amplified and sequenced using the serum sample. MEGA X and BLAST were used to analyze the sequencing results. The study's findings demonstrated that the APOA-1 gene length in samples of dyslipidemic patients and normal controls was 433 bp. While the normal control samples have the same sequence as the database, the dyslipidemic patient samples have an APOA-1 gene polymorphism in the promoter region. APOA-1 gene polymorphism results in disturbances in lipid profiles, particularly HDL which is at risk of developing dyslipidemia. The APOA-1 gene has the potential to be developed as a biomarker for diagnosing dyslipidemia involving a larger number of samples.

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References

Al-bustan, S. A., Al-serri, A. E., Annice, B. G., Alnaqeeb, M. A., & Ebrahim, G. A. (2013). Re-sequencing of the APOAI promoter region and the genetic association of the -75G > A polymorphism with increased cholesterol and low density lipoprotein levels among a sample of the Kuwaiti population. BMC Medical Genetics, 14(1), 1. https://doi.org/10.1186/1471-2350-14-90

Asif, S., Khan, M., Waqar Arshad, M., & Shabbir, M. I. (2021). PCR Optimization for Beginners: A Step by Step Guide. Research in Molecular Medicine, 9(2), 81–102. https://doi.org/10.32598/rmm.9.2.1189.1

Asselbergs, F. W., Guo, Y., Van Iperen, E. P. A., Sivapalaratnam, S., Tragante, V., Lanktree, M. B., … Drenos, F. (2012). Large-Scale Gene-Centric Meta-analysis Across 32 Studies Identifies Multiple Lipid Loci. American Journal of Human Genetics, 91(5), 823–838. https://doi.org/10.1016/j.ajhg.2012.08.032

de Grooth, G. J., Klerkx, A. H. E. ., Stroes, E. S. G., Stalenhoef, A. F. H., Kastelein, J. J. P., & Kuivenhoven, J. A. (2004). A review of CETP and its relation to atherosclerosis. Journal Lipid Research, 45(11), 1967–1974. https://doi.org/10.1194/jlr.R400007-JLR200

Eldeeb, M. A., Zaki, A. S., Ashour, S., Abdel Nasser, A., El Bassiouny, A., & Abdulghani, K. O. (2020). Serum Apolipoprotein A1: a Predictor and Prognostic Biomarker in Acute Ischemic Stroke. Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 56(3). https://doi.org/10.1186/s41983-019-0138-z

Fan, L., You, Y., Fan, Y., Shen, C., & Xue, Y. (2021). Association Between ApoA1 Gene Polymorphisms and Antipsychotic Drug-Induced Dyslipidemia in Schizophrenia. Neuropsychiatric Disease and Treatment, 17, 1289–1297. https://doi.org/10.2147/NDT.S305200

França, E. De, Alves, J. G. ., & Hutz, M. . (2005). APOA1 / C3 / A4 gene cluster variability and lipid levels in Brazilian children. Brazillian Journal of Medical and Biological Research, 38(4), 535–541. https://doi.org/10.1590/S0100-879X2005000400006

García-Giustiniani, D., & Stein, R. (2016). Genetics of dyslipidemia. Arquivos Brasileiros de Cardiologia, 106(5), 434–438. https://doi.org/10.5935/abc.20160074

Gene, M., Bora, K., Saikia, M., Borah, P., Hussain, I., & Das, D. (2016). Single nucleotide polymorphisms of APOA1 gene and their relationship with serum apolipoprotein A-I concentrations in the native population of Assam. Meta Gene, 7, 20–27. https://doi.org/10.1016/j.mgene.2015.10.005

Georgila, K., Vyrla, D., & Drakos, E. (2019). Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer. Cancers, 11(8), 1–26. https://doi.org/10.3390/cancers11081097

Haase, C. L., Tybjærg-hansen, A., Grande, P., & Frikke-schmidt, R. (2010). Genetically Elevated Apolipoprotein A-I, High-Density Lipoprotein Cholesterol Levels, and Risk of Ischemic Heart Disease. J Clin Endocrinol Metab, 95(12), 500–510. https://doi.org/10.1210/jc.2010-0450

Hedayatnia, M., Asadi, Z., Zare-feyzabadi, R., Yaghooti-khorasani, M., Ghazizadeh, H., Ghaffarian-zirak, R., … Ghayour-mobarhan, M. (2020). Dyslipidemia and cardiovascular disease risk among the MASHAD study population. Lipids in Health and Disease, 19(42), 1–11. https://doi.org/10.1186/s12944-020-01204-y

Hsu, L., & Lee, T. (2017). ScienceDirect Apolipoprotein A1 rs5070 A / G polymorphism with stroke subtypes in Taiwan. Journal of the Chinese Medical Association, 80(6), 360–365. https://doi.org/10.1016/j.jcma.2017.01.002

Jian, Z., Lung, C., Ko, P., Sun, Y., Huang, J., Ho, C., … Liaw, Y. (2013). The association between the apolipoprotein A1 / high density lipoprotein -cholesterol and diabetes in Taiwan — a cross-sectional study. BMC Endocrine Disorder, 13(42), 1–8. https://doi.org/10.1186/1472-6823-13-42

Kementerian Kesehatan Republik Indonesia. (2018). Hasil Riset Kesehatan Dasar Tahun 2018. Kementerian Kesehatan Republik Indonesia.

Kopin, L., & Lowenstein, C. (2017). In the Clinic Dyslipidemia. Annals of Internal Medicine, 167(11), ITC81–ITC95. https://doi.org/10.7326/AITC201712050

Liao, B. H., Cheng, K. Q., Dong, S. H., Liu, H. D., & Xu, Z. L. (2015). Effect of apolipoprotein A1 genetic polymorphisms on lipid profiles and the risk of coronary artery disease. Diagnostic Pathology, 10(1), 1–5. https://doi.org/10.1186/s13000-015-0328-7

Liu, S., Liu, J., Weng, R., Gu, X., & Zhong, Z. (2019). Apolipoprotein E gene polymorphism and the risk of cardiovascular disease and type 2 diabetes. BMC Cardiovascular Disorders, 19(213), 1–6. https://doi.org/10.1186/s12872-019-1194-0

Liu, T. N., Wu, C. T., He, F., Yuan, W., Li, S. X., Li, H. W., … Wu, M. (2016). Relationship between the G75A polymorphism in the apolipoprotein A1 (ApoA1) gene and the lipid regulatory effects of pravastatin in patients with hyperlipidemia. Genetics and Molecular Research, 15(2). https://doi.org/10.4238/gmr.15028216

Pagani, F., Sidoli, A., Giudici, G. A., Barenghi, L., Vergani, C., & Baralle, F. E. (1990). Human apolipoprotein A-I gene promoter polymorphism : association with hyperalp ha1 i poproteinemia. Journal Lipid Research, 31(8), 1371–1377. https://doi.org/10.1016/S0022-2275(20)42608-2

Pakdel, A., Reza, M., Eidgahi, A., & Bandegi, A. R. (2018). Association Between MspI Polymorphisms of the Apolipoprotein A-I Gene and Hyperlipidemia in an Iranian Population. Middle East J Rehabil Helath Stud, 5(1), 26–29. https://doi.org/10.5812/mejrh.60496.Research

Pandith, A. A., Bhat, I. A., Niyaz, I., Qasim, I., Bhat, I. A., Manzoor, U., & Koul, A. M. (2021). Association of APOA1-75G/A and+ 83C/T polymorphic variation with acute coronary syndrome patients in Kashmir (India). Journal of Cardiovascular and Thoracic Research, 13(2), 109.–115. https://doi.org/10.34172/jcvtr.2021.09

Rashad, N. M., Ebrahem, G. A., El-shal, A. S., Zenar, M. R. H. A.-, Ahmed, I. G., & Hamed, M. G. (2021). Association of Apolipoprotein A1 Gene Polymorphism and Coronary Heart Diseases in Patients with Type 2 Diabetes Mellitus. The Eguptian Journal of Hospital Medicine, 82(2), 289–295. https://doi.org/10.21608/ejhm.2021.143897

Rojas, M. P., Prieto, C., Bermúdez, V., Garicano, C., Nava, T. N., Martínez, M. S., ... & Rojas, J. (2017). Dyslipidemia: Genetics, lipoprotein lipase and HindIII polymorphism. F1000Research, 6. https://doi.org/10.12688/f1000research.12938.1

Shioji, K., Mannami, Æ. T., Kokubo, Æ. Y., Goto, Y., Nonogi, H., & Iwai, N. (2004). An association analysis between ApoA1 polymorphisms and the high-density lipoprotein ( HDL ) cholesterol level and myocardial infarction ( MI ) in Japanese. J Hum Genet, 49, 433–439. https://doi.org/10.1007/s10038-004-0172-1

Smach, M. A., Edziri, H., Charfeddine, B., Othman, L. Ben, Lammouchi, T., Ltaief, A., … Limem, K. (2012). Polymorphism in apoA1 Influences High-Density Lipoprotein Cholesterol Levels but Is Not a Major Risk Factor of Alzheimer ’ s Disease. Dement Geriatr Cogn Disord Extra, 1, 249–257. https://doi.org/10.1159/000329910

Smith, J. D., Brinton, E. A., & Breslow, J. L. (1992). Polymorphism in the human apolipoprotein AI gene promoter region. Association of the minor allele with decreased production rate in vivo and promoter activity in vitro. The Journal of clinical investigation, 89(6), 1796-1800. https://doi.org/ 10.1172/JCI115783

Stover, N. A., & Cavalcanti, A. R. O. (2017). Using NCBI BLAST. Current Protocols in Essential Laboratory Techniques, 2017(May), 11.1.1-11.1.34. https://doi.org/10.1002/cpet.8

Urry, L. A., Meyers, N., Cain, M. L., Wasserman, S. A., Minorsky, P. V., Orr, R., ... & Campbell, N. A. (2021). Campbell biology: Australian and New Zealand version. Pearson Australia.

Wang, Yanmei, Lu, Z., Zhang, J., Yang, Y., Shen, J., Zhang, X., & Song, Y. (2016). The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women. Lipids in Health and Disease, 15(170), 1–9. https://doi.org/10.1186/s12944-016-0343-z

Wang, Yanzhe, Liu, F., Li, L., Deng, S., & He, Z. (2017). The association between apolipoprotein A1-C3-A5 gene cluster promoter polymorphisms and risk of ischemic stroke in the northern Chinese Han population. Journal of International Medical Research, 45(6), 2042–2052. https://doi.org/10.1177/0300060517713517

Westfall, P. J., Pitera, D. J., Lenihan, J. R., Eng, D., Woolard, F. X., & Regentin, R. (2012). Production of amorphadiene in yeast , and its conversion to dihydroartemisinic acid , precursor to the antimalarial agent artemisinin. PNAS, 109(3), 111–118. https://doi.org/10.1073/pnas.1110740109

WHO. (2019). WHO Updates Cardiovascular Risk Charts. WHO

Xu, L., Zhou, Y., Yao, J., Sun, S., Rui, Q., Yang, X., & Li, X. (2017). Apolipoprotein A1 polymorphisms and risk of coronary artery disease : a meta-analysis. Arch Med Sci, 4, 813–819.

Xu, X., Song, Z., Mao, B., & Xu, G. (2022). Review Article Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy : Recent Progress and Future Perspectives. Cardiovascular Therapeutics. https://doi.org/10.1155/2022/4610834