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2019, Number 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

Language: Spanish
References: 30
Page: 58-62
PDF size: 349.97 Kb.


ABSTRACT

The ataxin 2 gene is a target in the pathogenesis of complex diseases, including cardiovascular risk factors and neurodegenerative diseases. ATXN2 gen has VNTR in exon 1, whose expansion exceeding 30 repetitions leads to the development of spinocerebellar ataxia type 2; lower-range repetitions are associated with type 2 diabetes or amyotrophic lateral sclerosis. This locus is also linked with metabolic and inflammatory phenotypes. In conclusion, this gene can be used as a clinical marker of metabolic and neurological phenotypes, which is related to its pleiotropic effect.


REFERENCES

  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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