Publicado
Genotypic frequency of the APOE gene polymorphism and its association with lipid profile and inflammatory markers in students from a university in Pereira, Colombia
Frecuencia genotípica del polimorfismo del gen APOE y su relación con el perfil lipídico y marcadores inflamatorios en estudiantes universitarios de Pereira, Colombia
DOI:
https://doi.org/10.15446/revfacmed.v72n2.111289Palabras clave:
Apolipoproteins E, Mutation, Lipids, Inflammation Mediators, Students (en)Apolipoproteínas E, Mutación, Lípidos, Mediadores de inflamación, Estudiantes (es)
Descargas
Introduction: Apolipoprotein E (ApoE) enables serum lipid clearance. Its polymorphism has been associated with dyslipidemia which, if persistent, leads to a proinflammatory state and the subsequent development of atherosclerosis.
Objective: To determine the genotypic frequency of the APOE gene polymorphism and to evaluate its association with lipid profile and inflammatory markers in university students from Pereira (Risaralda, Colombia).
Materials and methods: A descriptive cross-sectional study was carried out in 77 university students. Sociodemographic and anthropometric variables, ApoE polymorphism, lipid profile, and inflammatory markers were analyzed by means of questionnaires, body measurements, and blood samples. A bivariate analysis was performed to evaluate the association between the presence of dyslipidemia and the levels of inflammatory markers, sex, weekly physical activity level, and dietary pattern.
Results: The mean age of the participants was 19 years and 62.34% were women. The most frequent polymorphism was ApoE rs429358 C/T (100%), followed by ApoE rs7412 C/C (97.40%), and ApoE rs7412 C/T (2.60%). All parameters assessed in the lipid profile, as well as IL-1β and IL-6, were higher in ApoE rs7412 C/C genotype carriers than in ApoE rs7412 C/T carriers. Furthermore, 70.13% had dyslipidemia. Levels of IL-1β, IL-6, and TNFα were higher in participants with dyslipidemia than in individuals without this condition, but the differences were not statistically significant.
Conclusion: The ApoE rs429358 C/T polymorphism was expressed in all participants, suggesting a genetic predisposition to dementia and cardiovascular and cerebrovascular diseases according to the literature. ApoE rs7412 C/C carriers showed higher levels in all lipid profile parameters, IL-1β, and IL-6, demonstrating that lipid profile and inflammation markers are linked to the specific expression of APOE gene genotypes.
Introducción. La apolipoproteína E (ApoE) permite el aclaramiento sérico de lípidos; su polimorfismo se ha asociado con dislipidemia que, si persiste, conduce a un estado proinflamatorio y al subsecuente desarrollo de aterosclerosis.
Objetivos. Determinar la frecuencia genotípica del polimorfismo del gen APOE y evaluar su relación con el perfil lipídico y marcadores inflamatorios en estudiantes universitarios en Pereira (Risaralda, Colombia).
Materiales y métodos. Estudio trasversal descriptivo realizado en 77 estudiantes universitarios. Se analizaron las variables sociodemográficas, antropométricas, polimorfismo de ApoE, perfil lipídico y marcadores inflamatorios mediante cuestionarios, mediciones físicas y muestras de sangre. Se realizó un análisis bivariado para evaluar la asociación entre la presencia de dislipidemia y niveles de marcadores inflamatorios, sexo, nivel de actividad física semanal y patrón dietético.
Resultados. La edad media fue 19 años y 62.34% eran mujeres. El polimorfismo más frecuente fue ApoE rs429358 C/T (100%), seguido de ApoE rs7412 C/C (97.40%) y ApoE rs7412 C/T (2.60%). Todos los parámetros evaluados en el perfil lipídico, así como la IL-1β y la IL-6, fueron más altos en los portadores del genotipo ApoE rs7412 C/C que en los portadores de ApoE rs7412 C/T. Además, 70.13% tenían dislipidemia. Los niveles de IL-1β, IL-6 y TNFα fueron más altos en los participantes con dislipidemia que en aquellos sin esta condición, pero las diferencias no fueron estadísticamente significativas.
Conclusión. El polimorfismo ApoE rs429358 C/T fue expresado en todos los participantes, sugiriendo una predisposición genética a demencia y enfermedades cardiovasculares y cerebrovasculares según la literatura. Los portadores de ApoE rs7412 C/C mostraron niveles más altos en todos los parámetros del perfil lipídico, IL-1β e IL-6, demostrando que el perfil lipídico y los marcadores de la inflamación están ligados a la expresión específica de los genotipos del gen APOE.
Referencias
1. Mutlu AS, Duffy J, Wang MC. Lipid metabolism and lipid signals in aging and longevity. Dev Cell. 2021;56(10):1394-407. https://doi.org/gknq4n.
2. Real JT, Ascaso JF. Metabolismo lipídico y clasificación de las hiperlipemias. Clin Investig Arterioscler. 2021;33(Suppl 1):3-9. https://doi.org/nfjg.
3. Husain MA, Laurent B, Plourde M. APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics. Front Neurosci. 2021;15. https://doi.org/gmx9b4.
4. Yang LG, March ZM, Stephenson RA, Narayan PS. Apolipoprotein E in lipid metabolism and neurodegenerative disease. Trends Endocrinol Metab. 2023;34(8):430-45. https://doi.org/nd7s.
5. Bea AM, Larrea-Sebal A, Marco-Benedi V, Uribe KB, Galicia-Garcia U, Lamiquiz-Moneo I, et al. Contribution of APOE Genetic Variants to Dyslipidemia. Arterioscler Thromb Vasc Biol. 2023;43(6):1066-77. https://doi.org/nd7v.
6. Martínez S, Ochoa B, Pérez MR, Torrico F, García I, Garcia CC. Polimorfismos del gen de la apolipoproteína E en adultos mayores de 60 años con disminución de la memoria cognitiva y enfermedad de Alzheimer en diferentes poblaciones venezolanas. Biomedica. 2022;42(Sppl 1):116-29. https://doi.org/nd73.
7. Abondio P, Sazzini M, Garagnani P, Boattini A, Monti D, Franceschi C, et al. The Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity. Genes (Basel). 2019;10(3):222. https://doi.org/gf2q28.
8. Macedoni M, Hovnik T, Plesnik E, Kotnik P, Bratina N, Battelino T, et al. Metabolic control, ApoE genotypes, and dyslipidemia in children, adolescents and young adults with type 1 diabetes. Atherosclerosis. 2018;273:53-8. https://doi.org/gdmnb3.
9. Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, et al. Genome-Wide Association Study of NAFLD Using Electronic Health Records. Hepatol Commun. 2022;6(2):297-308. https://doi.org/nfjh.
10. Marais AD. Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease. Pathology. 2019;51(2):165-76. https://doi.org/gg5dr4.
11. Shao A, Shi J, Liang Z, Pan L, Zhu W, Liu S, et al. Meta-analysis of the association between Apolipoprotein E polymorphism and risks of myocardial infarction. BMC Cardiovasc Disord. 2022;22(1):126. https://doi.org/nd75.
12. Karjalainen J-P, Mononen N, Hutri-Kähönen N, Lehtimäki M, Juonala M, Ala-Korpela M, et al. The effect of apolipoprotein E polymorphism on serum metabolome - a population-based 10-year follow-up study. Sci Rep. 2019;9(1):458. https://doi.org/nd76.
13. Khalil YA, Rabès J-P, Boileau C, Varret M. APOE gene variants in primary dyslipidemia. Atherosclerosis. 2021;328:11-22. https://doi.org/gj55c3.
14. Jebari-Benslaiman S, Galicia-García U, Larrea-Sebal A, Olaetxea JR, Alloza I, Vandenbroeck K, et al. Pathophysiology of Atherosclerosis. Int J Mol Sci. 2022;23(6):3346. https://doi.org/gtr2t7.
15. Jiang X, Wang F, Wang Y, Gisterå A, Roy J, Paulsson-Berne G, et al. Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity. JACC Basic Transl Sci. 2019;4(3):304-17. https://doi.org/gh8vw9.
16. Silvain J, Kerneis M, Zeitouni M, Lattuca B, Galier S, Brugier D, et al. Interleukin-1β and Risk of Premature Death in Patients With Myocardial Infarction. J Am Coll Cardiol. 2020;76(15):1763-73. https://doi.org/gsfp8j.
17. MedlinePlus. APOE gene: apolipoprotein E. Bethesda, MD: National Library of Medicine. [cited 2022 May 1]. Available from: https://medlineplus.gov/genetics/gene/apoe/.
18. World Health Organization (WHO). The top 10 causes of death. Geneva: WHO; 2022 [cited 2022 May 1]. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
19. Jaramillo-Correa JP, Keyeux G, Ruiz-García M, Rodas C, Bernal J. Population genetic analysis of the genes APOE, APOB(3’VNTR) and ACE in some black and Amerindian communities from Colombia. Hum Hered. 2001;52(1):14-33. https://doi.org/bp6pq8.
20. Forero DA, Pinzón J, Arboleda GH, Yunis JJ, Alvarez C, Cataño N, et al. Analysis of common polymorphisms in angiotensin-converting enzyme and apolipoprotein e genes and human longevity in Colombia. Arch Med Res. 2006;37(7):890-4. https://doi.org/crvztz.
21. Perdomo VA, Ortega DC, Barreto G. Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia. Rev Colomb Psiquiatr (Engl Ed). 2020;51(2):99-104. https://doi.org/nfbq.
22. Ruiz M, Arias I, Rolón G, Hernández E, Garavito P, Silvera-Redondo C. Análisis del polimorfismo del gen APOE en la población de Barranquilla, Colombia. Biomedica. 2016;36(1):52-8. https://doi.org/nfbr.
23. Loango N, Gallego ML, Restrepo B, Landázuri P. Diferencias de sexo, edad y lípidos plasmáticos asociadas al polimorfismo de la apolipoproteína E en un grupo de escolares de Quindío, Colombia. Biomedica. 2009;29(3):382-91. https://doi.org/nfbs.
24. Rivera N, Perdomo VA, Barreto G. Frecuencias polimorficas del gen de Apolipoproteina E en el Valle del Cauca, Colombia. Revista de Ciencias. 2015;19(1):53-62. https://doi.org/nfbt.
25. Velez-Pardo C, Rojas W, Jimenez-Del Río M, Bedoya G. Distribution of APOE polymorphism in the “Paisa” population from northwest Colombia (Antioquia). Ann Hum Biol. 2015;42(2):195-8. https://doi.org/nfbv.
26. Rengifo L, Gaviria D, Serrano H. Polimorfismos del gen ApoE en individuos con síndrome de Down y sus progenitores en una población colombiana. Biomedica. 2012;32(2):224-32. https://doi.org/nfjj.
27. Sikand G, Severson T. Top 10 dietary strategies for atherosclerotic cardiovascular risk reduction. Am J Prev Cardiol. 2020;4:100106. https://doi.org/gqxjrp.
28. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502. https://doi.org/ghjc4x.
29. 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. https://doi.org/c275.
30. World Medical Association (WMA). WMA Declaration of Helsinki – Ethical principles for medical research involving human subjects. Fortaleza: 64th WMA General Assembly; 2013.
31. Colombia. Ministerio de Salud. Resolución 8430 de 1993 (octubre 4): Por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud. Bogotá D.C.; october 4 1993.
32. Chen XF, Wei Z, Wang T, Zhang ZL, Wang Y, Heckman MG, et al. Demographic and Lifestyle Characteristics, but Not Apolipoprotein E Genotype, Are Associated with Intelligence among Young Chinese College Students. PLoS One. 2015;10(11):e0143157. https://doi.org/nfc6.
33. Huang W, Zeng J, Jia L, Zhu D, O’Brien J, Ritchie C, et al. Genetic risks of Alzheimer’s by APOE and MAPT on cortical morphology in young healthy adults. Brain Commun. 2023;5(5):fcad234. https://doi.org/nfc7.
34. Li X, Kaur Y, Wilhelm O, Reuter M, Montag C, Sommer W, et al. Resting-state brain signal complexity discriminates young healthy APOE e4 carriers from non-e4 carriers. Eur J Neurosci. 2023;57(5):854-66. https://doi.org/nfc8.
35. Lissaman R, Lancaster TM, Parker GD, Graham KS, Lawrence AD, Hodgetts CJ. Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study. Neuroimage Rep. 2022;2(4):100126. https://doi.org/nfg4.
36. Doliner B, Dong C, Blanton SH, Gardener H, Elkind MSV, Sacco RL, et al. Apolipoprotein E Gene Polymorphism and Subclinical Carotid Atherosclerosis: The Northern Manhattan Study. J Stroke Cerebrovasc Dis. 2018;27(3):645-52. https://doi.org/nfhb.
37. Lioutas VA, Beiser AS, Aparicio HJ, Himali JJ, Selim MH, Romero JR, et al. Assessment of Incidence and Risk Factors of Intracerebral Hemorrhage Among Participants in the Framingham Heart Study Between 1948 and 2016. JAMA Neurol. 2020;77(10):1252-60. https://doi.org/gjjxhp.
38. Wu H, Huang Q, Yu Z, Wu H, Zhong Z. The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population. Lipids Health Dis. 2020;19(1):202. https://doi.org/nfhf.
39. Peng W, Liu J, Chen G, Zheng M, Zhang L, Li A, et al. The correlation between ApoE gene polymorphism and non-ischemic chronic heart failure. Int J Clin Exp Med. 2017;10(12):16809-14.
40. Ghaznavi H, Kiani AA, Soltanpour MS. Association study between DNA methylation and genetic variation of APOE gene with the risk of coronary artery disease. Mol Biol Res Commun. 2018;7(4):173-9. https://doi.org/nfhj.
41. Stocker H, Trares K, Beyer L, Perna L, Rujescu D, Holleczek B, et al. Alzheimer’s polygenic risk scores, APOE, Alzheimer’s disease risk, and dementia-related blood biomarker levels in a population-based cohort study followed over 17 years. Alzheimers Res Ther. 2023;15(1):129. https://doi.org/nfhk.
42. Nuinoon M, Saiphak W, Nawaka N, Rattanawan C, Pussadhamma B, Jeenduang N. Association of CELSR2, APOB100, ABCG5/8, LDLR, and APOE polymorphisms and their genetic risks with lipids among the Thai subjects. Saudi J Biol Sci. 2023;30(2):103554. https://doi.org/nfhn.
43. Fan YY, Cai QL, Gao ZY, Lin X, Huang Q, Tang W, et al. APOE ε4 allele elevates the expressions of inflammatory factors and promotes Alzheimer’s disease progression: A comparative study based on Han and She populations in the Wenzhou area. Brain Res Bull. 2017;132:39-43. https://doi.org/gbpz5v.
44. Lainampetch J, Panprathip P, Phosat C, Chumpathat N, Prangthip P, Soonthornworasiri N, et al. Association of Tumor Necrosis Factor Alpha, Interleukin 6, and C-Reactive Protein with the Risk of Developing Type 2 Diabetes: A Retrospective Cohort Study of Rural Thais. J Diabetes Res. 2019;2019:9051929. https://doi.org/nfht.
45. Hong N, Lin Y, Ye Z, Yang C, Huang Y, Duan Q, et al. The relationship between dyslipidemia and inflammation among adults in east coast China: A cross-sectional study. Front Immunol. 2022;13:937201. https://doi.org/nfh6.
46. Galvis-Pérez Y, Barona-Acevedo J, Cardona-Arias JA. Prevalencia de dislipidemias en una institución prestadora de servicios de salud de Medellín (Colombia), 2013. Rev CES Med. 2016;30(1):3-13.
47. Cardona-Arias JA. Prevalencia de factores de riesgo cardiovascular en indígenas de Riosucio-Caldas, 2010-2011. Medicina UPB. 2012;31:113-26.
Dimensions
PlumX
Visitas a la página del resumen del artículo
Descargas
Cómo citar
Licencia
Derechos de autor 2024 Revista de la Facultad de Medicina
Esta obra está bajo una licencia Creative Commons Reconocimiento 3.0 Unported.
-
