APOE gene is a genetic determinant for alteration of lipid profiles in obesity

Authors

  • พิสชา ชาญณรงค์ Master of Science Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University
  • สุวรรณี ชั้นประเสริฐโยธิน Research & Innovation, Faculty of Medicine Ramathibodi Hospital, Mahidol University
  • พัชรา แพนพันธ์อ้วน Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University
  • รจนา ชุณหบัณฑิต Graduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University
  • กอบเกียรติ ดอนสกุล Health Office, Electricity Generating Authority of Thailand
  • ธันยชัย สุระ Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University
  • ปิยะมิตร ศรีธรา Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University
  • จินตนา ศิริวราศัย Graduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University

Keywords:

APOE, Polymorphism, Obesity, Dyslipidemia, TaqMan real-time PCR

Abstract

Apolipoprotein E (ApoE) is a component of lipoprotein that plays role in lipid metabolism by acting as ligand binding lipoprotein with hepatocyte cell-surface receptors to clearance of chylomicrons and VLDL. Genetic study revealed an association of ApoE gene (APOE) with dyslipidemia and CVD. To investigate association between APOE polymorphism (rs7412 and rs429358) and serum lipid levels in obesity, 93 control persons and 314 obese persons, aged between 45-65 years were recruited from the Electricity Generating Authority of Thailand (EGAT) Cohort study in 2013. Genotypes of APOE polymorphism were analyzed by TaqMan real-time PCR. In control group, genotype frequencies of ε2/ε2, ε2/ε3, ε3/ε3, ε2/ε4, ε3/ε4 and ε4/ε4 were 2.2%, 17.2%, 62.4%, 3.2%, 15.1% and 0%, respectively. Allele frequencies of ε2, ε3 and ε4 were 0.12, 0.79 and 0.09, respectively. For obese group, genotype frequencies of ε2/ε2, ε2/ε3, ε3/ε3, ε2/ε4, ε3/ε4 and ε4/ε4 were 1.3%, 18.8%, 55.4%, 5.4%, 17.8% and 1.3% respectively. Allele frequencies of ε2, ε3 and ε4 were 0.13, 0.74 and 0.13, respectively. The APOE polymorphism showed influences on serum lipid levels in obese group. Individuals with ε4/ε4 genotype in obese group had higher TC than ε2/ε4 and higher LDL-C than ε2/ε3, ε3/ε3 and ε2/ε4 genotypes. Additionally, carriers with ε3/ε4 showed significantly higher LDL-C than ε2/ε4 genotype. In conclusion, association between APOE polymorphism and serum lipid profiles in obese is existed and this gene may be a useful genetic determinant for obesity and dyslipidemiaas well as cardiovascular disease in Thais.

References

1. Alexander CM, Landsman PB, Grundy SM. The influence of age and body mass index on the metabolic syndrome and its components. Diabetes Obes Metab. 2008;10(3):246-50.

2. Klop B, Elte JWF, Cabezas MC. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients. 2013;5(4):1218-40.

3. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2015-2016. NCHS Data Brief. 2017;288.

4. Global Health Observatory. Global Health Observatory data [internet]. 2016 [cited 2017 May 15]. Available from: https://www.who.int/gho/ncd/risk_ factors/overweight/en/.

5. Aekplakorn W, Mo-suwan L. National prevalence of obesity: prevalence of obesity in Thailand. Obes Rev. 2009;10:589-92.

6. Heller DA, de Faire U, Pedersen NL, Dahlén G, McClearn GE. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med. 1993;328:1150-6.

7. Mahley RW, Huang Y, Rall SC Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia).Questions, quandaries, and paradoxes. J Lipid Res. 1999;40(11):1933-49.

8. Kolovou GD, Anagnostopoulou KK, Kostakou P, Giannakopoulou V, Mihas C, Hatzigeorgiou G, et al. Apolipoprotein E gene polymorphism and obesity status in middle-aged men with coronary heart disease. In Vivo. 2009;23(1):33-9.

9. Huang Y, Mahley RW. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases. Neurobiol Dis. 2014;72:3-12.

10. Cahua-Pablo G, Cruz M, Moral-Hernández OD, Leyva-Vázquez MA, Antúnez-Ortiz DL, Cahua-Pablo JA, et al. Elevated levels of LDL-C are associated with ApoE4 but not with the rs688 polymorphism in the LDLR gene. Clin Appl Thromb Hemost. 2016;22(5):465-70.

11. Marques-Vidal P, Bongard V, Ruidavets JB, Fauvel J, Hanaire-Broutin H, Perret B, et al. Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on lipids and insulin. Obes Res. 2003;11(10):1200-6.

12. Klop B, Elte JW, Cabezas MC. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients. 2013;5(4):1218–40.

13. Decharatkulchai N, Settasatian C, Settasatian N, Komanasin N, Leelayuwat N, Sirijaichingkul S, et al. Apolipoprotein E polymorphism and dyslipidemia in Thais. J Med Tech Phy Ther. 2009;21:141-52.

14. WHO/IOTF/IASO. The Asia-Pacific perspective: redefining obesity and its treatment. Australia: World Health Organization Regional Office for the Western Pacific; 2000.

15. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) final report. Circulation. 2002;106(25):3143-421.

16. Rashid S, Genest J. Effect of obesity on high-density lipoprotein metabolism. Obesity. 2007;15(12):2875-88.

17. Brinton EA, Terry JG. Increased intra-abdominal fat maylower HDL levels by increasing the fractional catabolic rate of lipoprotein A-I in postmenopausal women. Circulation. 1996;94(Suppl):I-266.

18. Opie LH. Metabolic syndrome. Circulation. 2007;115(3):32-5.

19. Wilson PW, D'Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162(16):1867-72.

20. Agrawal N, Agrawal MK, Kumari T, Kumar S. Correlation between Body Mass Index and Blood Glucose Levels in Jharkhand Population. IJCMR. 2017;4(8):1633-6.

21. Belfort R, Mandarino L, Kashyap S, Wirfel K, Pratipanawatr T, Berria R, et al. Dose-response effect of elevated plasma free fatty acid on insulin signalling. Diabetes. 2005;54:164-8.

22. Capurso C, Capurso A. From excess adiposity to insulin resistance: the role of free fatty acids. Vascul Pharmacol. 2012;57:91-7.

23. Chanprasertyothin S, Ongphiphadhanakul B, Rajatanavin R, Piaseu N, Chailurkit LO, Puavilai G. Correlation of apolipoprotein E gene polymorphism to serum lipid concentrations in healthy Thais. J Med Assoc Thai. 2000;83(10):1233-9.

24. Chaudhary R, Likidlilid A, Peerapatdit T, Tresukosol D, Srisuma S, Ratanamaneechat S, et al. Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovasc Diabetol. 2012;11(36):1-11.

25. Boulenouar H, Mediene Benchekor S, Meroufel DN, Lardjam Hetraf SA, Ouhaib iDjellouli H, Hermant X, et al. Impact of APOE gene polymorphisms on the lipid profile in an Algerian population. Lipids Health Dis. 2013;12(155):1-8.

26. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988;8(1):1-21.

27. Schaefer EJ, Lamon-Fava S, Jenner JL, McNamara JR, Ordovas JM, Davis CE, et al. Lipoprotein(a) levels and risk of coronary heart disease in men. JAMA. 1994;271(13):999-1003.

28. Phillips MC. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014;66(9):616-23.

29. Chaichanawongsaroj N, Yingsiwapat W, Chaingchong W. The effect of exercise on plasma lipid concentrations varies with Apo E genotype: a study in Thais subject. J Med Tech Assoc Thailand. 2006;34(3):1655-66.

30. Shin MH, Kim HN, Cui LH, Kweon SS, Park KS, Heo H. The effect of apolipoprotein E polymorphism on lipid levels in Korean adults. J Korean Med Sci. 2005;20(3):361-6.

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Published

2018-06-30

How to Cite

ชาญณรงค์ พ., ชั้นประเสริฐโยธิน ส., แพนพันธ์อ้วน พ., ชุณหบัณฑิต ร., ดอนสกุล ก., สุระ ธ., ศรีธรา ป., & ศิริวราศัย จ. (2018). APOE gene is a genetic determinant for alteration of lipid profiles in obesity. Journal of Nutrition Association of Thailand, 53(1), 1–14. Retrieved from https://he01.tci-thaijo.org/index.php/JNAT/article/view/126987

Issue

Vol. 53 No. 1 (2018): January-June

Section

Research article

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Upon acceptance of an article, copyright is belonging to the Nutrition Association of Thailand.