Asociación entre el gen de caveolina 1 (cav1) y el riesgo cardiovascular en adultos

  • Gustavo Mora García Universidad de Cartagena
  • María Stephany Ruiz Díaz Universidad de Cartagena
  • Ángelo Alario Bello Universidad de Cartagena
  • Doris Gómez Camargo Universidad de Cartagena
  • Claudio Gómez Alegría Universidad Nacional de Colombia

Resumen

La caveolina 1 es una proteína estructural que interviene en diversos procesos metabólicos. En estudios de asociación genética, el gen que la codifica CAV1 (7q31.2) se ha asociado a resistencia a la insulina, hipertensión, hipertrigliceridemia y c-HDL bajo. Sin embargo, se desconoce si variantes en CAV1 se asocian a obesidad e incremento en el riesgo cardiovascular (RCV).


Objetivo: Analizar la posible asociación entre variantes en CAV1 con el RCV en población del caribe colombiano.
Metodología: Se realizó un estudio de asociación genética con 595 adultos de Cartagena de Indias. Se hizo la genotipificación de los polimorfismos de nucleótido simple (SNPs): rs3779512, rs926198, rs10207569, rs11773845, rs7804372, rs1049337. El RCV fue definido mediante el puntaje derivado del estudio de Framingham. Para estimar la asociación entre las variables de estudio se realizó un análisis de varianza ajustado y fueron construidos árboles de regresión. Se aplicó el ajuste de Bonferroni para pruebas múltiples, donde fuera necesario.
Resultados: La variante rs1049337 se encontró asociada con el incremento del RCV (p=0,0001). Los sujetos con el genotipo TT en este locus tuvieron un mayor puntaje de RCV, +4,1 IC95% [0,8-8,0] en comparación con CC (p=0,03) y +4,3 IC95% [0,3-8,4] con CT (p=0,03). El árbol mostró que en el grupo TT (rs1049337) presentaba un mayor puntaje si los sujetos además contaban con el genotipo TT para rs3779512.
Conclusiones: Las variantes rs1049337 y rs3779512 se encuentran asociadas a incremento en el puntaje de RCV.

##plugins.generic.usageStats.downloads##

##plugins.generic.usageStats.noStats##

Biografía del autor

##submission.authorWithAffiliation##

Medicina, Doctorado en Medicina Tropical. Universidad de Cartagena, Cartagena de Indias, Colombia.

##submission.authorWithAffiliation##

Medicina, Estudiante del Doctorado en Medicina Tropical. Universidad de Cartagena, Cartagena de Indias, Colombia. Internista.

##submission.authorWithAffiliation##

Medicina, Medicina Interna. Universidad de Cartagena, Cartagena de Indias, Colombia.

##submission.authorWithAffiliation##

Bacterióloga, Maestría en Microbiología Clínica, Doctorado enBiología Molecular. Universidad de Cartagena, Cartagena de Indias, Colombia. 

##submission.authorWithAffiliation##

Bioquímica, Doctorado en Ciencias Biológicas, Postdoctorado. Universidad Nacional de Colombia, Bogotá, Colombia.

Citas

1. World Health Organization. Global Atlas on Cardiovascular Disease Prevention and Control: World Health Organization; 2013.
2. Goff DC, Jr., Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S49-73.
3. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016. European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). European heart journal. 2016;37(29):2315-81.
4. Fernando L, Pamela S, Alejandra L. Cardiovascular disease in Latin America: the growing epidemic. Progress in cardiovascular diseases. 2014;57(3):262-7.
5. World Health Organization. Global status report on noncommunicable diseases 2014. Geneva: World Health Organization; 2014. 280 p. p.
6. Amouyel P, Deverly A. [Global cardiovascular risk: definition, evaluation and management strategies. Round table no. 1. XV]. Therapie. 2000;55(4):533-9.
7. deGoma EM, Dunbar RL, Jacoby D, French B. Differences in absolute risk of cardiovascular events using risk-refinement tests: a systematic analysis of four cardiovascular risk equations. Atherosclerosis. 2013;227(1):172-7.
8. Sotos-Prieto M, Baylin A, Campos H, Qi L, Mattei J. Lifestyle Cardiovascular Risk Score, Genetic Risk Score, and Myocardial Infarction in Hispanic/Latino Adults Living in Costa Rica. Journal of the American Heart Association. 2016;5(12).
9. Humphries SE, Cooper JA, Talmud PJ, Miller GJ. Candidate gene genotypes, along with conventional risk factor assessment, improve estimation of coronary heart disease risk in healthy UK men. Clinical chemistry. 2007;53(1):8-16.
10. Morrison AC, Bare LA, Chambless LE, Ellis SG, Malloy M, Kane JP, et al. Prediction of coronary heart disease risk using a genetic risk score: the Atherosclerosis Risk in Communities Study. American journal of epidemiology. 2007;166(1):28-35.
11. Bolton JL, Stewart MC, Wilson JF, Anderson N, Price JF. Improvement in prediction of coronary heart disease risk over conventional risk factors using SNPs identified in genome-wide association studies. PloS one. 2013;8(2):e57310.
12. Beaney KE, Cooper JA, Ullah Shahid S, Ahmed W, Qamar R, Drenos F, et al. Clinical Utility of a Coronary Heart Disease Risk Prediction Gene Score in UK Healthy Middle Aged Men and in the Pakistani Population. PloS one. 2015;10(7):e0130754.
13. Companioni O, Rodriguez Esparragon F, Fernandez-Aceituno AM, Rodriguez Perez JC. [Genetic variants, cardiovascular risk and genome-wide association studies]. Revista espanola de cardiologia. 2011;64(6):509-14.
14. Mora Garcia G, Gomez Alegria C, Gomez Camargo D. Caveolin 1 (CAV1) gene polymorphisms associated to body mass index, hypertension and obesity related disorders in adults from Caribbean population. Obesity Reviews. 2016;17(Suppl. 2):5 - 20.
15. Engelman JA, Zhang XL, Lisanti MP. Sequence and detailed organization of the human caveolin-1 and -2 genes located near the D7S522 locus (7q31.1). Methylation of a CpG island in the 5’ promoter region of the caveolin-1 gene in human breast cancer cell lines. FEBS letters. 1999;448(2-3):221-30.
16. Kurzchalia TV, Dupree P, Monier S. VIP21-Caveolin, a protein of the trans- Golgi network and caveolae. FEBS letters. 1994;346(1):88-91.
17. Yamada E. The fine structure of the gall bladder epithelium of the mouse. The Journal of biophysical and biochemical cytology. 1955;1(5):445-58.
18. Liu GZ, Liang B, Lau WB, Wang Y, Zhao J, Li R, et al. High glucose/High Lipids impair vascular adiponectin function via inhibition of caveolin-1/AdipoR1 signalsome formation. Free radical biology & medicine. 2015;89:473-85.
19. Baudrand R, Goodarzi MO, Vaidya A, Underwood PC, Williams JS, Jeunemaitre X, et al. A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics. Metabolism: clinical and experimental. 2015;64(12):1674-81.
20. Pojoga LH, Underwood PC, Goodarzi MO, Williams JS, Adler GK, Jeunemaitre X, et al. Variants of the caveolin-1 gene: a translational investigation linking insulin resistance and hypertension. The Journal of clinical endocrinology and metabolism. 2011;96(8):E1288-92.
21. Grilo A, Fernandez ML, Beltran M, Ramirez-Lorca R, Gonzalez MA, Royo JL, et al. Genetic analysis of CAV1 gene in hypertension and metabolic syndrome. Thrombosis and haemostasis. 2006;95(4):696-701.
22. Razani B, Combs TP, Wang XB, Frank PG, Park DS, Russell RG, et al. Caveolin- 1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. The Journal of biological chemistry. 2002;277(10):8635-47.
23. Gomez Camargo D, Camacho-Mejorado R, Gomez Alegria C, Alario Bello A, Hernandez-Tobias EA, Mora Garcia G, et al. Genetic structure of Cartagena de Indias population using hypervariable markers of Y chromosome. Open Journal of Genetics. 2015;5(1):1-20.
24. Builes JJ, Martinez B, Gomez A, Caraballo L, Espinal C, Aguirre D, et al. Y chromosome STR haplotypes in the Caribbean city of Cartagena (Colombia). Forensic science international. 2007;167(1):62-9.
25. Noguera MC, Schwegler A, Gomes V, Briceno I, Alvarez L, Uricoechea D, et al. Colombia’s racial crucible: Y chromosome evidence from six admixed communities in the Department of Bolivar. Ann Hum Biol. 2014;41(5):453-9.
26. Vergara C, Murray T, Rafaels N, Lewis R, Campbell M, Foster C, et al. African ancestry is a risk factor for asthma and high total IgE levels in African ad- mixed populations. Genetic epidemiology. 2013;37(4):393-401.
27. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366(9491):1059-62.
28. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA : the journal of the American Medical Association. 2014;311(5):507-20.
29. D’Agostino RB, Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framing- ham Heart Study. Circulation. 2008;117(6):743-53.
30. Gregory Warnes and with contributions from Gregor Gorjanc and Friedrich Leisch and Michael Man. (2013). genetics: Population Genetics. R package version 1.3.8.1. https://CRAN.R-project.org/package=genetics.
31. Terry Therneau BAaBR. rpart: Recursive Partitioning and Regression Trees. R package version 4.1-10. https://CRAN.R-project.org/package=rpart.
32. R Core Team (2016). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org/.
33. Liu L, Ebana Y, Nitta JI, Takahashi Y, Miyazaki S, Tanaka T, et al. Genetic Variants Associated With Susceptibility to Atrial Fibrillation in a Japanese Population. Can J Cardiol. 2017;33(4):443-9.
34. Asker S, Taspinar M, Koyun H, Ozbay B, Arisoy A. Caveolin-1 polymorphisms in patients with severe obstructive sleep apnea. Biomarkers. 2017;22(1):77-80.
35. Zhao R, Liu K, Huang Z, Wang J, Pan Y, Huang Y, et al. Genetic Variants in Caveolin-1 and RhoA/ROCK1 Are Associated with Clear Cell Renal Cell Carcinoma Risk in a Chinese Population. PloS one. 2015;10(6):e0128771.
36. Langeberg WJ, Tahir SA, Feng Z, Kwon EM, Ostrander EA, Thompson TC, et al. Association of caveolin-1 and -2 genetic variants and post-treatment serum caveolin-1 with prostate cancer risk and outcomes. Prostate.
2010;70(9):1020-35.
37. Liu Y, Hauser MA, Akafo SK, Qin X, Miura S, Gibson JR, et al. Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry. Invest Ophthalmol Vis Sci. 2013;54(9):6248-54.
38. Rong SS, Chen LJ, Leung CK, Matsushita K, Jia L, Miki A, et al. Ethnic specific association of the CAV1/CAV2 locus with primary open-angle glaucoma. Sci Rep. 2016;6:27837.
39. Wiggs JL, Kang JH, Yaspan BL, Mirel DB, Laurie C, Crenshaw A, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA. Hum Mol Genet. 2011;20(23):4707-13.
40. Chen YH, Lin WW, Liu CS, Hsu LS, Lin YM, Su SL. Caveolin-1 Expression Ameliorates Nephrotic Damage in a Rabbit Model of Cholesterol-Induced Hypercholesterolemia. PloS one. 2016;11(4):e0154210.
41. Roberts KE, Fallon MB, Krowka MJ, Brown RS, Trotter JF, Peter I, et al. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179(9):835-42.
42. Manetti M, Allanore Y, Saad M, Fatini C, Cohignac V, Guiducci S, et al. Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis. Ann Rheum Dis. 2012;71(6):1034-41.
43. Chen S, Wang X, Wang J, Zhao Y, Wang D, Tan C, et al. Genomic variant in CAV1 increases susceptibility to coronary artery disease and myocardial infarction. Atherosclerosis. 2016;246:148-56.
44. Shyu HY, Chen MH, Hsieh YH, Shieh JC, Yen LR, Wang HW, et al. Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke. PloS one. 2017;12(3):e0174110.
45. Kastelijn EA, van Moorsel CH, Kazemier KM, Roothaan SM, Ruven HJ, Kwak- kel-van Erp JM, et al. A genetic polymorphism in the CAV1 gene associates with the development of bronchiolitis obliterans syndrome after lung transplantation. Fibrogenesis Tissue Repair. 2011;4:24.
46. Shiroto T, Romero N, Sugiyama T, Sartoretto JL, Kalwa H, Yan Z, et al. Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium. PloS one. 2014;9(2):e87871.
47. Williams JJ, Palmer TM. Cavin-1: caveolae-dependent signalling and cardiovascular disease. Biochem Soc Trans. 2014;42(2):284-8.
Publicado
2018-03-18
##submission.howToCite##
MORA GARCÍA, Gustavo et al. Asociación entre el gen de caveolina 1 (cav1) y el riesgo cardiovascular en adultos. Revista Colombiana de Endocrinología, Diabetes & Metabolismo, [S.l.], v. 5, n. 1, p. 15-21, mar. 2018. ISSN 2389-9786. Disponible en: <http://www.revistaendocrino.org/index.php/rcedm/article/view/337>. Fecha de acceso: 20 sep. 2020
Sección
Articulos Originales