Apolipoprotein E Gene Polymorphism and Its Association with Cardiovascular Heart Disease Risk Factors in Type 2 Diabetes Mellitus
Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The APOE ɛ3 allele was the most common one in both groups. There was no significant association between the APOE genotypes and the CAD status in Type 2 DM using Pearson χ2 test. Further analysis indicated there were no significant differences in all lipid parameters between E2, E3 and E4 subgroups in both groups. The study showed that the E4 allele carriers of Type 2 DM with CAD patients had higher LDL-C level and lower HDL-C level compared to the other allele carriers. However, analyses showed these levels were not statistically different. The study also showed that the Type 2 DM with CAD group with E2 allele had higher triglyceride (TG). In conclusion, further study with larger sample size is needed to confirm role of E4 as a marker of CAD among Type 2 DM patients in Malaysian population.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1127432Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 870
 Sicree R, Shaw, J. & Zimmet, P: Prevalence and projections. Diabetes atlas 2006:16-104.
 Letchuman GR, Wan Nazaimoon WM, Wan Mohamad WB, Chandran LR, Tee GH, Jamaiyah H, Isa MR, Zanariah H, Fatanah I, Ahmad Faudzi Y: Prevalence of diabetes in the Malaysian National Health Morbidity Survey III 2006. Med J Malaysia 2010; 65:180-6.
 Cade WT: Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 2008; 88:1322-35.
 Syvanne M, Taskinen MR: Lipids and lipoproteins as coronary risk factors in non-insulin-dependent diabetes mellitus. Lancet 1997; 350 Suppl 1:SI20-3.
 Chew BH, Ismail, M., Lee, P. Y., Taher, S. W., Haniff, J., Mustapha, F. I. & Bujang, M. A: Determinants of uncontrolled dyslipidaemia among adult type 2 diabetes in Malaysia: the Malaysian Diabetes Registry 2009. diabetes research and clinical practice 2012; 96:339-47. .
 Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U, Danesh J: Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007; 298:1300-11.
 Damani SB, Topol EJ: Emerging genomic applications in coronary artery disease. JACC Cardiovasc Interv 2011; 4:473-82.
 Hixson JE, Vernier DT: Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. Journal of Lipid Research 1990; 31:545-8.
 Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-97.
 Klein R: Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995; 18:258-68.
 Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR: Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998; 316:823-8.
 Standl E, Balletshofer B, Dahl B, Weichenhain B, Stiegler H, Hormann A, Holle R: Predictors of 10-year macrovascular and overall mortality in patients with NIDDM: the Munich General Practitioner Project. Diabetologia 1996; 39:1540-5.
 Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405-12.
 Dyslipidemia Management in Adults With Diabetes. Diabetes Care 2003; 27:s68-s71.
 Mohamed E, Mohamed M, Rashid FA: Dyslipidaemic pattern of patients with type 2 diabetes mellitus. Malays J Med Sci 2004; 11:44-51.
 Cook CB, Erdman DM, Ryan GJ, Greenlund KJ, Giles WH, Gallina DL, El-Kebbi IM, Ziemer DC, Ernst KL, Dunbar VG, Phillips LS: The pattern of dyslipidemia among urban African-Americans with type 2 diabetes. Diabetes Care 2000; 23:319-24.
 Burman D, Mente A, Hegele RA, Islam S, Yusuf S, Anand SS: Relationship of the ApoE polymorphism to plasma lipid traits among South Asians, Chinese, and Europeans living in Canada. Atherosclerosis 2009; 203:192-200.
 Mamotte CDS, Burke V, Taylor RR, van Bockxmeer FM: Evidence of reduced coronary artery disease risk for apolipoprotein ϵ2/3 heterozygotes. European Journal of Internal Medicine 2002; 13:250-5.
 Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csazar A, Utermann G: The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Am J Hum Genet 1991; 49:338-49.
 Muros M, Rodríguez-Ferrer C: Apolipoprotein E polymorphism influence on lipids, apolipoproteins and Lp(a) in a Spanish population underexpressing apo E4. Atherosclerosis 1996; 121:13-21.
 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.
 Morbois-Trabut L, Chabrolle C, Garrigue MA, Lasfargues G, Lecomte P: Apolipoprotein E genotype and plasma lipid levels in Caucasian diabetic patients. Diabetes Metab 2006; 32:270-5.
 Seet WT, Mary Anne TJ, Yen TS: Apolipoprotein E genotyping in the Malay, Chinese and Indian ethnic groups in Malaysia-a study on the distribution of the different apoE alleles and genotypes. Clin Chim Acta 2004; 340:201-5.
 Vaisi-Raygani A, Rahimi Z, Nomani H, Tavilani H, Pourmotabbed T: The presence of apolipoprotein epsilon4 and epsilon2 alleles augments the risk of coronary artery disease in type 2 diabetic patients. Clin Biochem 2007; 40:1150-6.
 Wilson PW, Schaefer EJ, Larson MG, Ordovas JM: Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler Thromb Vasc Biol 1996; 16:1250-5.
 Koch W, Hoppmann P, Schomig A, Kastrati A: Apolipoprotein E gene epsilon2/epsilon3/epsilon4 polymorphism and myocardial infarction: case-control study in a large population sample. Int J Cardiol 2008; 125:116-7.
 Letonja M, Guzic-Salobir B, Peterlin B, Petrovic D: Apolipoprotein E gene polymorphism effects triglycerides but not CAD risk in Caucasian women younger than 65 years. Ann Genet 2004; 47:147-53.
 Hashim Y, Shepherd D, Wiltshire S, Holman RR, Levy CJ, Clark A, Cull AC: Butyrylcholinesterase K variant on chromosome 3 q is associated with Type II diabetes in white Caucasian subjects. Diabetologia 2001; 44:2227-30.
 Singh PP, Naz I, Gilmour A, Singh M, Mastana S: Association of APOE (Hha1) and ACE (I/D) gene polymorphisms with type 2 diabetes mellitus in North West India. Diabetes Res Clin Pract 2006; 74:95-102.
 Ginsberg HN: New Perspectives on Atherogenesis. Circulation 2002; 106:2137.
 Balcerzyk A, Zak I, Krauze J: Synergistic effects of apolipoprotein E gene epsilon polymorphism and some conventional risk factors on premature ischaemic heart disease development. Kardiol Pol 2007; 65:1058-65; discussion 66-7.
 Topic A, Spasojevic Kalimanovska V, Zeljkovic A, Vekic J, Jelic Ivanovic Z: Gender-related effect of apo E polymorphism on lipoprotein particle sizes in the middle-aged subjects. Clin Biochem 2008; 41:361-7.
 Jemaa R, Elasmi M, Naouali C, Feki M, Kallel A, Souissi M, Sanhaji H, Hadj Taïeb S, Souheil O, Kaabachi N: Apolipoprotein E polymorphism in the Tunisian population: Frequency and effect on lipid parameters. Clin Biochem 2006; 39:816-20.
 Malloy SI, Altenburg MK, Knouff C, Lanningham-Foster L, Parks JS, Maeda N: Harmful effects of increased LDLR expression in mice with human APOE*4 but not APOE*3. Arterioscler Thromb Vasc Biol 2004; 24:91-7.
 Gensini GF, Comeglio M, Colella A: Classical risk factors and emerging elements in the risk profile for coronary artery disease. Eur Heart J 1998; 19 Suppl A:A53-61.
 Joss N, Jardine A, Gaffney D, Boulton-Jones JM: Influence of apolipoprotein E genotype on progression of diabetic nephropathy. Nephron Exp Nephrol 2005; 101:e127-33.