Volume: 43 Issue: 1
Year: 2023, Page: 433-438, Doi: https://doi.org/10.51248/.v43i01.2408
Introduction and Aim: The ApoE gene polymorphisms are considered as risk factors for developing atherosclerosis and related cardiovascular disease (CVD) in humans. There exists no study pertaining to ApoE gene polymorphism and its association to these disorders among the Iraqi population. Hence in this study, we aimed to investigate the possible relationship between single nucleotide polymorphisms (SNPs) in the ApoE gene with the prevalence of diabetes (T2DM) and cardiovascular disease among the Iraqi population.
Materials and Methods: This cross-sectional investigation involved 76 patients (50 with diabetics and 26 with cardiovascular disease) and 73 otherwise healthy individuals. The ApoE gene fragment corresponding to the SNPs rs429358 and rs7412 was amplified using conventional polymerase chain reaction (PCR) with a specific pair of primers. Genotyping was performed by direct sequencing.
Results: Differences in genotypic and allelic frequencies were seen in SNPs rs429358 and rs7412 of the ApoE gene. Significant higher frequency was seen for the CT genotype in SNP rs429358 when compared to healthy controls. Among the epsilon alleles, the ε3/ε3 was the most common genotype, accounting for 76% and 69.23% of patients with diabetes and CVD, respectively. ε2/ε4 was the least common genotype, accounting for 2% and 0% of diabetes and CVD patients, respectively. When DM patients were compared to controls, the genotype ε 3 ε 4 was found to be more common in T2DM patients (10%) than in controls (1.34%), with a significant difference (OR= 4.32, 95%CI=0.02-0.98, p= 0.050). At the allelic level, the ε2 allele was significantly more common in patients than in controls (OR= 12.73, 95%CI= 1.38-116.87).
Conclusion: Data in this study indicate ApoE gene polymorphisms in SNPs rs429358 and rs7412 could be risk factors for T2DM and CVD in Iraqi patients.
Keywords: Apoprotein E; type 2 diabetes mellitus; cardiovascular disease; gene polymorphism
1. Miao, J., Zang, X., Cui, X., Zhang, J. Autophagy, hyperlipidaemia, and atherosclerosis. Adv Exp Med Biol. 2020; 1207:237-264.
2. Meng, Q., Zhang, X. H., Zhang, X. W. Meta-analysis on association of ApoE gene polymorphism with hyperlipidaemia. Chinese Preventive Med. 2015; 16:304-307.
3. Zhao, X. N., Sun, Q., Cao, Y. Q. Association between apolipoprotein gene polymorphisms and hyperlipidaemia: a meta-analysis. BMC Genom Data 2021; 22, 14 doi.org/10.1186/s12863-021-00968-1
4. Cai, C., Wen, Z., Li, L. The relationship between Apo E gene polymorphism and the efficacy of statins controlling hyperlipidaemia. Am J Transl Res. 2021; 13(6): 6772–6777.
5. Boot, C. S., Luvai, A., Neely, R. D. G. The clinical and laboratory investigation of dysbetalipoproteinemia. Critical Reviews in Clinical Laboratory Sciences. 2020; 57(7):458-469.
13. van Bockxmeer, F. M., Mamotte, C. D. Apolipoprotein epsilon 4 homozygosity in young men with coronary heart disease. Lancet 1992; 340:879-880.
14. Kumar, P., Luthra, K., Dwivedi, M., Behl, V. K., Pandey, R. M., Misra, A. Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India. Ann Clin Biochem 2003, 40:382-387.
15. Guang-da, X., You-ying, L., Zhi-song, C., Yu-sheng, H., Xiang-jiu, Y. Apolipoprotein e4 allele is a predictor of coronary artery disease death in elderly patients with type 2 diabetes mellitus. Atherosclerosis. 2004; 175:77-81.
16. Clark, D., Skrobot, O., Adebiyi, I., Susce, M., De Leon, J., Blakemore, A., Arranz, M. Apolipoprotein-E gene variants associated with cardiovascular risk factors in antipsychotic recipients. Eur. Psychiatry. 2009; 24(7): 456-463.
17. Zheng, Y. M., Sun, R., Li, X. Y., Zhu, D., Gao, M., Zhao, L. B., et al., Relationship between ApoE gene polymorphism and type 2 diabetes mellitus with its cardiovascular complications in Chinese. Chin. J. Endocrinol. Metab. 1998;14: 11-14.
18. Chaaba, R., Attia, N., Hammami, S., Smaoui, M., Ben Hamda, K., Mahjoub, S., et al., Association between apolipoprotein E polymorphism, lipids, and coronary artery disease in Tunisian type 2 diabetes. J. Clin. Lipidol. 2008; 2:360-364.
19. Halim, E. F., Reda, A. A., Hendi, A. A., Zaki, S. A., Essa, E. S., Khalifa, A. S. Apolipoprotein E gene variants as a risk factor for coronary artery disease in type 2 diabetic Egyptian patients. Egypt. J. Immunol. 2012; 19:1-10.
20. Guo, J. J., Ju J., Xu, X. H. Association of polymorphisms of apolipoprotein E gene and high-sensitive C-reactive protein with type 2 diabetes with coronary heart disease. Shaanxi Med. J. 2007; 36:1613-1616.
21. Song, Y., Stampfer, M. J., Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann. Intern. Med. 2004; 141:137-147.
22. Xu, M., Zhao, J., Zhang, Y., Ma, X., Dai, Q., Zhi, H., et al., Apolipoprotein E gene variants and risk of coronary heart disease: a meta-analysis. Biomed Res. Int. 2016; 2016:3912175.
23. Zhang, M. D., Gu, W., Qiao, S. B., Zhu, E. J., Zhao, Q. M., Lv, S. Z. Apolipoprotein E gene polymorphism and risk for coronary heart disease in the Chinese population: a meta-analysis of 61 studies including 6634 cases and 6393 controls. PLoS ONE 2004; 9:e95463.
24. Zhang, Y., Tang, H. Q., Peng, W. J., Zhang, B. B., Liu, M. Meta analysis for the association of apolipoprotein E epsilon2/epsilon3/epsilon4 polymorphism with coronary heart disease. Chin. Med. J. 2015;128: 1391-1398.
25. Wu, Z. R., Chen, Z. C., Fu, M. X., Chen, J. Y., Han, L. Y., Zhou, L. H., et al., Polymorphism of apolipoprotein E gene and type 2 diabetic patients with coronary heart disease among Chinese Han population: a meta-analysis. J. Clin. Exp. Med. 2015; 14:982-985
6. Hameed, S. T., Al-Mayah, Q. S., Khudeir, M. S., Al-Shamma, G. A. Estimation of dysbetalipoproteinemia incidence in Iraqi patients with diabetes mellitus and cardiovascular disease. PJMHS 2022; 16:469-472.
7. Bennet, A. M., Di Angelantonio, E., Ye, Z., Wensley, F., Dahlin, A., Ahlbom, A., et al., Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 2007 Sep 19; 298(11):1300-1311.
8. Larifla, L., Armand, C., Bangou, J., Blanchet-Deverly, A., Numeric, P., Fonteau, C., et al., Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans. PLoS ONE 2007; 12:e0181620. doi:10.1371/journal.pone.0181620
9. Hou, J., Deng, Q., Guo, X., Deng, W., Zhong, W., Zhong, Z. Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China. Lipids Health Dis, 2020; 19, 139, doi.org/10.1186/s12944-020-01323-6
10. Liu, S., Liu, J., Weng, R., Gu, X., Zhong, Z. Apolipoprotein E gene polymorphism and the risk of cardiovascular disease and type 2 diabetes. BMC Cardiovasc Disord. 2019; 19(1):213-219.
11. Al-Jaf, S. frequencies of Apolipoprotein E polymorphism in Iraqi Kurdish population. Biology Metagene 2021; 28: 6. doi.10.1016/J.MGENE.2021.100867.
12. Eichner, J. E., Kuller, L. H., Orchard, T. J., Grandits, G. A., McCallum, L. M., Ferrell, R. E., et al., Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease. Am J Cardiol 1993; 71:160-165.
Samar T. Hameed, Qasim S. Al-Mayah, Mahmood S. Khudhair, Ghassan A. Al-Shamma. Apoprotein-E gene polymorphism in an Iraqi population with type 2 diabetes and cardiovascular disease. Biomedicine: 2023; 43(1): 433-438