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ISSN 0016-3813 (Impreso)

2019, Número 1

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Gac Med Mex 2019; 155 (1)


Ataxina-2, nuevo blanco en enfermedades genéticas complejas

Ramírez-García SA, Sánchez-Corona J, Ortega-Pacheco D, Ramírez-Bohórquez E, García-Cruz D

Idioma: Español
Referencias bibliográficas: 30
Paginas: 58-62
Archivo PDF: 349.97 Kb.


RESUMEN

El gen de la ataxina-2 es un blanco en la patogénesis de enfermedades complejas, entre ellas los factores de riesgo cardiovascular y enfermedades neurodegenerativas. El gen ATXN2 tiene un VNTR en el exón 1, cuya expansión por encima de las 30 repeticiones provoca al desarrollo de ataxia espinocerebelosa tipo 2; las repeticiones en rango menor se asocian con diabetes tipo 2 o esclerosis lateral amiotrófica. También este locus está ligado con fenotipos metabólicos e inflamatorios. En conclusión, el gen puede ser utilizado como marcador clínico de fenotipos metabólicos y neurológicos, lo cual está relacionado con su efecto pleiotrópico.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Nkiliza A, Chartier-Harlin MC. ATXN2 a culprit with multiple facets. Oncotarget. 2017;8:34028-34029.

  2. Lastres-Becker I, Rüb U, Auburger G. Spinocerebellar ataxia 2 (SCA2). Cerebellum. 2008;7:115-124.

  3. Fittschen M, Lastres-Becker I, Halbach MV, Damrath E, Gispert S, Azizov M, et al. Genetic ablation of ataxin-2 increases several global translation factors in their transcript abundance but decreases translation rate. Neurogenetics. 2015;16:181-192.

  4. Ma L, Hanson RL, Traurig MT, Muller YL, Kaur BP, Perez JM, et al. Evaluation of A2BP1 as an obesity gene. Diabetes. 2010;59:2837-2845.

  5. Figueroa KP, Farooqi S, Harrup K, Frank J, O’Rahilly S, Pulst SM. Genetic variance in the spinocerebellar ataxia type 2 (ATXN2) gene in children with severe early onset obesity. PLoS One. 2009;4:e8280.

  6. Kiehl TR, Nechiporuk A, Figueroa KP, Keating MT, Huynh DP, Pulst SM. Generation and characterization of Sca2 (ataxin-2) knockout mice. Biochem Biophys Res Commun. 2006;339:17-24.

  7. Lastres-Becker I, Nonis D, Eich F, Klinkenberg M, Gorospe M, Kötter P, et al. Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by starvation. Biochim Biophys Acta. 2016;1862:1558-1569.

  8. Lastres-Becker I, Brodesser S, Lütjohann D, Azizov M, Buchmann J, Hintermann E, et al. Insulin receptor and lipid metabolism pathology in ataxin-2 knock-out mice. Hum Mol Genet. 2008;17:1465-1481.

  9. Drost J, Nonis D, Eich F, Leske O, Damrath E, Brunt E, et al. Ataxin-2 modulates the levels of Grb2 and Src but not Ras signaling. J Mol Neurosci. 2013;51:68-81.

  10. Auburger G, Gispert S, Lahut S, Omür O, Damrath E, Heck M, et al. 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? World J Diabetes. 2014;5:316-327.

  11. Flores-Alvarado LJ, Dávalos-Rodríguez NO, García-Cruz D, Madrigal- Ruiz PM, Ruiz-Mejía R, Aguilar-Aldrete ME, et al. (CAG)n polymorphism of the ATXN2 gene, a new marker of susceptibility for type 2 diabetes mellitus. Rev Panam Salud Publica. 2016;40:318-324.

  12. Kraja AT, Chasman DI, North KE, Reiner AP, Yanek LR, Kilpeläinen TO, et al. Pleiotropic genes for metabolic syndrome and inflammation. Mol Genet Metab. 2014;112 317-338.

  13. Zhang H, Mo XB, Xu T, Bu XQ, Lei SF, Zhang YH. Novel genes affecting blood pressure detected via gene-based association analysis. G3 (Bethesda). 2015;5:1035-1042.

  14. Soranzo N, Spector TD, Mangino M, Kühnel B, Rendon A, Teumer A, et al. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet. 2009;41:1182-1190.

  15. Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, et al. Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. PLoS Genet. 2010;6:e1001184.

  16. Ganesh SK, Zakai NA, Van-Rooij FJ, Soranzo N, Smith AV, Nalls MA, et al. Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nat Genet. 2009;41:1191-1198.

  17. Meierhofer D, Halbach M, Şen NE, Gispert S, Auburger G. Ataxin-2 (Atxn2)-knock-out mice show branched chain amino acids and fatty. Mol Cell Proteomics. 2016;15:1728-1739.

  18. Abdel-Aleem A, Zaki MS. Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy. J Neurol. 2008;255:413-419.

  19. Huynh DP, Maalouf M, Silva AJ, Schweizer FE, Pulst SM. Dissociated fear and spatial learning in mice with deficiency of ataxin-2. PLoS One. 2009;4:e6235.

  20. Scoles DR, Meera P, Schneider MD, Paul S, Dansithong W, Figueroa KP, et al. Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Nature. 2017;544 362-366.

  21. Li PP, Sun X, Xia G, Arbez N, Paul S, Zhu S, et al. ATXN2-AS, a gene antisense to ATXN2, is associated with spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis. Ann Neurol. 2016;80:600-615.

  22. Wild PS, Felix JF, Schillert A, Teumer A, Chen MH, Leening MJG, et al. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. J Clin Invest. 2017;127:1798-1812.

  23. Khurana V, Peng J, Chung CY, Auluck PK, Fanning S, Tardiff DF, et al. Genome-scale networks link neurodegenerative disease genes to α-synuclein through specific molecular pathways. Cell Syst. 2017;4:157-170.

  24. Almaguer-Mederos LE, Almaguer-Gotay D, Aguilera-Rodríguez R, González- Zaldívar Y, Cuello-Almarales D, Laffita-Mesa J, et al. Association of glutathione S-transferase omega polymorphism and spinocerebellar ataxia type 2. J Neurol Sci. 2017;372 324-328.

  25. Ding D, Li K, Wang C, Chen Z, Long Z, Peng Y, et al. ATXN2 polymorphism modulates age at onset in Machado-Joseph disease. Brain. 2016;139(10):e59.

  26. Marthaler AG, Schmid B, Tubsuwan A, Poulsen UB, Engelbrecht AF, Mau-Holzmann UA, et al. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271.Stem Cell Res. 2016;16:180-183.

  27. Marthaler AG, Schmid B, Tubsuwan A, Poulsen UB, Hyttel P, Nielsen TT, et al. Generation of spinocerebellar ataxia type 2 patient-derived iPSC line H266. Stem Cell Res. 2016;16:166-169.

  28. Marthaler AG, Tubsuwan A, Schmid B, Poulsen UB, Hyttel P, Nielsen JE, et al. Generation of spinocerebellar ataxia type 2 patient-derived iPSC line H271. Stem Cell Res. 2016;16:159-161.

  29. Bailey JN, Loomis SJ, Kang JH, Allingham RR, Gharahkhani P, Khor CC, et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet. 2016;48:189-194.

  30. Halbach MV, Gispert S, Stehning T, Damrath E, Walter M, Auburger G. Atxn2 knock-out and CAG42-knock-in cerebellum shows similarly dysregulated expression in calcium homeostasis pathway. Cerebellum. 2017;16:68-81.




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