Genetic and Epigenetic Factors of E3/E3 Genotypes of APO-E Gene as a Strong Predictor for the Diagnosis of Coronary Artery Disease Patients of South India

Author(s): Javeed Ahmad Tantray, Karnati Pratap Reddy, Kaiser Jamil*, Waseem Gul Lone, Shiva Kumar Yerra.

Journal Name: Current Proteomics

Volume 17 , Issue 2 , 2020

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Abstract:

Background: The role of Apolipoprotein-E (APO-E) in lipid metabolism and cholesterol transport is a key component of lipid metabolism which plays a role in diseases like hypercholesterolemia, diabetes, and cardiovascular disease. The aim of this study was to determine the genotypes, allelic frequencies, gene expression and methylation related to apolipoprotein E polymorphism in Coronary Artery Disease (CAD) patients and compare with non-CAD healthy subjects of South Indian population.

Methods: The APO-E alleles and genotypes were determined by PCR-RFLP. Gene expression profiles for E3/E3 genotypes were determined using RT-PCR and methylation status was determined using Methyl Specific PCR assay in one hundred patients and an equal number of controls.

Results: Four APO-E genotypes (E4/E4, E3/E3, E3/E4, and E2/E3) were identified with different allele frequency. Among these, E3/E3 genotype and E3 allele were found to be significantly higher in cases than controls. The present study showed that the mRNA expression of APO-E was up-regulated in CAD patients with E3/E3 genotype in comparison with controls. Methylation status indicated a significant association of E3/E3 genotypes with the disease.

Conclusion: Different populations studied worldwide showed inherent variable frequencies of the APO-E alleles and genotypes, with the most frequent allele being E3. In this study, the APO-E genotypes E2/E3/E4 showed variable response to CAD, further, there was a significant association of E3/E3 genotypes to CAD risk; this genotype can be suggested for the diagnosis of CAD.

Keywords: Apolipoprotein-E, genotypes, alleles, gene expression, methylation, polymorphism, Coronary Artery Disease (CAD).

[1]
Miller, P.E.; Zhao, D.; Frazier-Wood, A.C.; Michos, E.D.; Averill, M.; Sandfort, V. Associations between coffee, tea, and caffeine intake with coronary artery calcification and cardiovascular events. Am. J. Med., 2016, 130(2), 188-197.
[http://dx.doi.org/10.1016/j.amjmed.2016.08.038] [PMID: 27640739]
[2]
Weber, T.; Lang, I.; Zweiker, R.; Horn, S.; Wenzel, R.R.; Watschinger, B.; Slany, J.; Eber, B.; Roithinger, F.X.; Metzler, B. Hypertension and coronary artery disease: Epidemiology, physiology, effects of treatment, and recommendations: A joint scientific statement from the Austrian society of cardiology and the Austrian society of hypertension. Wien. Klin. Wochenschr., 2016, 128(13-14), 467-479.
[http://dx.doi.org/10.1007/s00508-016-0998-5] [PMID: 27278135]
[3]
Mahley, R.W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science, 1988, 240(4852), 622-630.
[http://dx.doi.org/10.1126/science.3283935] [PMID: 3283935]
[4]
Ewbank, D.C. Differences in the association between apolipoprotein E genotype and mortality across populations. J. Gerontol. A Biol. Sci. Med. Sci., 2007, 62(8), 899-907.
[http://dx.doi.org/10.1093/gerona/62.8.899] [PMID: 17702883]
[5]
Lamarche, B.; Moorjani, S.; Lupien, P.J.; Cantin, B.; Bernard, P.M.; Dagenais, G.R.; Després, J.P. Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Québec cardiovascular study. Circulation, 1996, 94(3), 273-278.
[http://dx.doi.org/10.1161/01.CIR.94.3.273] [PMID: 8759066]
[6]
Mora, S.; Otvos, J.D.; Rifai, N.; Rosenson, R.S.; Buring, J.E.; Ridker, P.M. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation, 2009, 119(7), 931-939.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.816181] [PMID: 19204302]
[7]
Tantray, J.A.; Reddy, K.P.; Jamil, K.; Kumar, Y.S. Pharmacodynamic and cytogenetic evaluation in CYP2C19*2 and CYP2C19*3 allelomorphism in South Indian population with clopidogrel therapy. Int. J. Cardiol., 2017, 229, 113-118.
[http://dx.doi.org/10.1016/j.ijcard.2016.11.217] [PMID: 27915083]
[8]
Braun, T.R.; Been, L.F.; Singhal, A.; Worsham, J.; Ralhan, S.; Wander, G.S.; Chambers, J.C.; Kooner, J.S.; Aston, C.E.; Sanghera, D.K. A replication study of GWAS-derived lipid genes in Asian Indians: The chromosomal region 11q23.3 harbors loci contributing to triglycerides. PLoS One, 2012, 7(5)e37056
[http://dx.doi.org/10.1371/journal.pone.0037056] [PMID: 22623978]
[9]
Chaudhary, R.; Likidlilid, A.; Peerapatdit, T.; Tresukosol, D.; Srisuma, S.; Ratanamaneechat, S.; Sriratanasathavorn, C. Apolipoprotein E gene polymorphism: Effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovasc. Diabetol., 2012, 11, 36.
[http://dx.doi.org/10.1186/1475-2840-11-36] [PMID: 22520940]
[10]
Mayor, S. High cholesterol diet is not linked to increased heart risk, study shows. BMJ, 2016, 352, i919.
[http://dx.doi.org/10.1136/bmj.i919] [PMID: 26880021]
[11]
Ghebranious, N.; Ivacic, L.; Mallum, J.; Dokken, C. Detection of ApoE2, E3 and E4 alleles using maldi-tof mass spectrometry and the homogeneous mass-extend technology. Nucleic Acids Res., 2005, 33(17)e149
[http://dx.doi.org/10.1093/nar/gni155] [PMID: 16204452]
[12]
Jamil, K.; Kandula, V.; Kandula, R.; Asimuddin, M.; Joshi, S.; Yerra, S.K. Polymorphism of CYP3A4 2 and eNOS genes in the diabetic patients with hyperlipidemia undergoing statin treatment. Mol. Biol. Rep., 2014, 41(10), 6719-6727.
[http://dx.doi.org/10.1007/s11033-014-3557-z] [PMID: 24996290]
[13]
Lone, W.G.; Khan, I.A.; Poornima, S.; Shaik, N.A.; Meena, A.K.; Prabhakar Rao, K.; Hasan, Q. Exploration of CAG triplet repeat in nontranslated region of SCA12 gene. J. Genet., 2016, 95(2), 427-432.
[http://dx.doi.org/10.1007/s12041-016-0624-3] [PMID: 27350687]
[14]
Flegge, H.M. An investigation of the determination of serum cholesterol by an enzymatic method. Ann. Clin. Biochem., 1973, 10, 79-84.
[15]
Fossati, P.; Prencipe, L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin. Chem., 1982, 28(10), 2077-2080.
[PMID: 6812986]
[16]
Demacker, P.N.; Vos-Janssen, H.E.; Hijmans, A.G.; van’t Laar, A.; Jansen, A.P. Measurement of high-density lipoprotein cholesterol in serum: comparison of six isolation methods combined with enzymic cholesterol analysis. Clin. Chem., 1980, 26(13), 1780-1786.
[PMID: 6777082]
[17]
Jackson, R.; Chambless, L.; Higgins, M. Sex differences in ischemic heart disease mortality and risk factors in 46 communities: An etiologic analysis. Cardiovas. Risk Factors, 1997, 7, 43-54.
[18]
Mckeigue, P.M.; Adelstein, A.M.; Shipley, M.J.; Riemersma, R.A.; Mamot, M.G.; Hunt, S.P. Diet and risk factors for coronary heart disease in Asian in North west London. Lancet, 1985, 1086-1090.
[19]
Tantray, J.A.; Reddy, K.P.; Jamil, K.; Kumar, Y.S. Typical findings of epidemiological and clinical characteristics of patients with coronary artery diseases in South India: A retrospective analysis. Int. J. Med. Sci. Public Health, 2017, 6(1), 123-128.
[http://dx.doi.org/10.5455/ijmsph.2017.15072016571]
[20]
Wilson, P.W. Diabetes mellitus and coronary heart disease. Am. J. Kidney Dis., 1998, 32(5)(Suppl. 3), S89-S100.
[http://dx.doi.org/10.1053/ajkd.1998.v32.pm9820468] [PMID: 9820468]
[21]
Venkatramana, R.; Chengal, R.; Ferrell, R.E. Apolipoprotein E polymorphism among the Indian populations and its comparison with other Asian populations. Int. J. Hum. Genet., 2001, 1(2), 123-128.
[http://dx.doi.org/10.1080/09723757.2001.11885746]
[22]
Sharma, P.; Kumar, J.; Garg, G.; Kumar, A.; Patowary, A.; Karthikeyan, G.; Ramakrishnan, L.; Brahmachari, V.; Sengupta, S. Detection of altered global DNA methylation in coronary artery disease patients. DNA Cell Biol., 2008, 27(7), 357-365.
[http://dx.doi.org/10.1089/dna.2007.0694] [PMID: 18613790]
[23]
Kim, M.; Long, T.I.; Arakawa, K.; Wang, R.; Yu, M.C.; Laird, P.W. DNA methylation as a biomarker for cardiovascular disease risk. PLoS One, 2010, 5(3)e9692
[http://dx.doi.org/10.1371/journal.pone.0009692] [PMID: 20300621]


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VOLUME: 17
ISSUE: 2
Year: 2020
Page: [147 - 153]
Pages: 7
DOI: 10.2174/1570164616666190724095158
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