medigraphic.com

2023, Número 2

<< Anterior Siguiente >>

Rev Hematol Mex 2023; 24 (2)


Adaptación hematológica del habitante andino a la altura

Amaru R, Quispe T, Mamani LF, Mancilla S, Valencia JC, Patón D, Carrasco M

Idioma: Español
Referencias bibliográficas: 32
Paginas: 52-67
Archivo PDF: 786.74 Kb.


RESUMEN

Antecedentes: Los aymaras andinos y tibetanos montañeses desde hace 14,000 y 44,000 años, respectivamente, han habitado regiones de gran altitud desarrollando variaciones genéticas, algunas relacionadas con fenotipos eritroides vinculados con la regulación de la eritropoyesis.
Objetivo: Evaluar la asociación de los haplotipos de genes EPAS1, EGLN1, PKLR y NFkB1 entre aymaras y tibetanos, además de su relación con la adaptación a la altura.
Materiales y Métodos: Estudio analítico longitudinal prospectivo sobre haplotipos EPAS1 (5 SNPs denisovan, 5 SNPs no-denisovan), EGLN1 (PHD2D4E, PHD2C127S), PKLR (7 SNPs) y NFkB1 (2 SNPs) presentes en aymaras andinos bolivianos y tibetanos montañeses. Los haplotipos también se clasificaron considerando las vías metabólicas de acción en que intervienen.
Resultados: Se observó que los aymaras andinos carecen de haplotipos EPAS1- denisovan y PHD2D4E, pero tienen 2 de 5 variantes EPAS1 no denisovan, baja prevalencia de PHD2C127S (forma heterocigota), PKLR 50% y NFkB1 91%.
Conclusiones: Aymaras y tibetanos tienen haplotipos que refieren patrones genéticos comunes, pero también haplotipos enriquecidos específicos; la frecuencia y la interacción de éstos en las vías metabólicas sugieren una adaptación hematológica parcial y completa, respectivamente.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Gonzales GF. Hemoglobina y testosterona: importancia enla aclimatación y adaptación a la altura. Rev Peru Med ExpSalud Pública 2011; 28 (1): 92-100.

  2. Noel-Jorand M, Burnet H. Changes in human respiratorysensation induced by acute high altitude hypoxia. Neuroreport1994; 5 (13): 1561-6. doi: 10.1097/00001756-199408150-00005.

  3. Hu H, Petousi N, Glusman G, Yu Y, Bohlender R, Tashi T, etal. Evolutionary history of Tibetans inferred from wholegenomesequencing. PLoS Genetics 2017; 13 (4). https://doi.org/10.1371/journal.pgen.1006675.

  4. Rademaker K, Hodgins G, Moore K, Zarrillo S, Miller C,Bromley GR, et al. Paleoindian settlement of the highaltitudePeruvian Andes. Science 2014; 346 (6208): 466-9.https://doi.org/10.1126/science.1258260.

  5. Julian CG, Moore LG. Human genetic adaptation to highaltitude: Evidence from the Andes. Genes 2019; 10 (2):150. doi: 10.3390/genes10020150.

  6. Beall CM, Cavalleri GL, Deng L, Elston RC, Gao Y, Knight J, etal. Natural selection on EPAS1 (HIF2α) associated with lowhemoglobin concentration in Tibetan highlanders. ProceedNational Acad Sci 2010; 107 (25): 11459-64. https://doi.org/10.1073/pnas.1002443107.

  7. Ronen R, Zhou D, Bafna V, Haddad GG. The genetic basis ofchronic mountain sickness. Physiology 2014; 29 (6): 403-12.doi: 10.1152/physiol.00008.2014.

  8. Simonson TS. Altitude adaptation: a glimpse through variouslenses. High Alt Med Biol 2015; 16 (2): 125-37. doi:10.1089/ham.2015.0033.

  9. Bigham AW, Lee FS. Human high-altitude adaptation:forward genetics meets the HIF pathway. Genes Dev 2014;28 (20): 2189-204. doi: 10.1101/gad.250167.114.

  10. Moore LG, Brewer GJ. Beneficial effect of rightward hemoglobin-oxygen dissociation curve shift for short-term highaltitudeadaptation. J Lab Clin Med 1981; 98 (1): 145-54.

  11. Dempsey JA. With hemoglobin as with politics‐should weshift right or left? J Physiol 2020. doi: 10.1113/JP279555.

  12. Milledge J. Hypobaria: High altitude, aviation physiology,and medicine. Cotes’ Lung Function 2020: 615-37.

  13. Semenza GL. The genomics and genetics of oxygenhomeostasis. Ann Rev Genomics Hum Genet 2020; 21:183-204. doi: 10.1146/annurev-genom-111119-073356.

  14. Samanta D, Semenza GL. Metabolic adaptation of cancerand immune cells mediated by hypoxia-inducible factors.Biochim Biophys Acta Rev Cancer 2018; 1870 (1): 15-22.doi: 10.1016/j.bbcan.2018.07.002.

  15. Tashi T, Reading NS, Wuren T, Zhang X, Moore LG, Hu H, etal. Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2α) polymorphismlowers hemoglobin concentration in Tibetan highlanders.J Mol Med 2017; 95 (6): 665-70. doi: 10.1007/s00109-017-1519-3.

  16. Prabhakar NR. 2019 Nobel Prize in Physiology or Medicine.Am Physiol Soc 2020. https://doi.org/10.1152/physiol.00001.2020.

  17. Chan X, Eoh J, Volkova E, Black R, Fang L, Gorashi R, et al. HIF2Again-of-function mutation modulates the stiffness of smoothmuscle cells and compromises vascular mechanics. iScience2021; 24 (4): 102246. doi: 10.1016/j.isci.2021.102246.

  18. Huerta-Sánchez E, Jin X, Bianba Z, Peter BM, VinckenboschN, Liang Y, et al. Altitude adaptation in Tibetans causedby introgression of Denisovan-like DNA. Nature 2014;512 (7513): 194-7. https://doi.org/10.1038/nature13408.

  19. Lorenzo FR, Huff C, Myllymäki M, Olenchock B, Swierczek S,Tashi T, et al. A genetic mechanism for Tibetan high-altitudeadaptation. Nature Genetics 2014; 46 (9): 951. https://doi.org/10.1038/ng.306.

  20. Simonson TS, Yang Y, Huff CD, Yun H, Qin G, WitherspoonDJ, et al. Genetic evidence for high-altitude adaptationin Tibet. Science 2010; 329 (5987): 72-5. doi: 10.1126/science.1189406.

  21. Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo ZXP, Pool JE, etal. Sequencing of 50 human exomes reveals adaptation tohigh altitude. Science 2010; 329 (5987): 75-8. doi: 10.1126/science.1190371.

  22. Amaru R, Song J, Reading NS, Gordeuk VR, Quispe T, MooreL, et al. Erythroid and cardiovascular high altitude-selectedhaplotypes in Andean aymaras and Tibetans. Blood. 2017;130 (Supplement 1): 2205. https://doi.org/10.1182/blood.V130.Suppl_1.2205.2205.

  23. Song J, Abello V, Amaru R, Sergueeva A, Isakova J, KosinskiPA, et al. Tibetan enriched PKLR variant is beneficial to highaltitude adaption by improving oxygen delivery. Blood2018; 132 (Supplement 1): 1027. https://doi.org/10.1182/blood-2018-99-117389.

  24. Bigham AW, Julian CG, Wilson MJ, Vargas E, Browne VA,Shriver MD, et al. Maternal PRKAA1 and EDNRA genotypesare associated with birth weight, and PRKAA1 with uterineartery diameter and metabolic homeostasis at high altitude.Physiol Genomics 2014; 46 (18): 687-97. doi: 10.1152/physiolgenomics.00063.2014.

  25. Amaru R, Amaru A, Miguez H, Gina T, Mamani J, Vera O, etal. Bolivian aymara natives with chronic mountain sicknesshave autonomous BFU-E growth. Blood 2015; 126: 5206.https://doi.org/10.1182/blood.V126.23.5206.5206.

  26. Song J, Han S, Amaru R, Quispe T, Kim D, Crawford JE, etal. Novel form of alternative splicing of NFKB1. Its role inpolycythemia and adaptation to high altitude in AndeanAymara. Blood 2018; 132 (Supplement 1): 2316. https://doi.org/10.1182/blood-2018-99-117463.

  27. Crawford JE, Amaru R, Song J, Julian CG, Racimo F, Cheng JY,et al. Natural selection on genes related to cardiovascularhealth in high-altitude adapted Andeans. Am J Human Genet2017; 101 (5): 752-67. doi: 10.1016/j.ajhg.2017.09.023.

  28. Figueroa Y, Chan AK, Ibrahim R, Tang Y, Burow ME, Alam J,Scandurro AB, Beckman BS. NF-kappaB plays a key role inhypoxia-inducible factor-1-regulated erythropoietin geneexpression Exp Hematol 2002; 30: 1419-27. doi: 10.1016/s0301-472x(02)00934-7.

  29. Chen P-S, Chiu W-T, Hsu P-L, Lin S-C, Peng I-C, Wang C-Y,et al. Pathophysiological implications of hypoxia in humandiseases. J Biomed Sci 2020; 27: 1-19. https://doi.org/10.1186/s12929-020-00658-7.

  30. Rees JS, Castellano S, Andrés AM. The genomics of humanlocal adaptation. Trends Genet 2020. doi: 10.1016/j.tig.2020.03.006.

  31. Key FM, Fu Q, Romagné F, Lachmann M, Andrés AM. Humanadaptation and population differentiation in the lightof ancient genomes. Nature Communications 2016; 7 (1):1-11. https://doi.org/10.1038/ncomms10775.

  32. Shestakova A, Lorenzo F, Tashi T, Lanikova L, WittwerCT, Prchal JT. Tibetan PHD2 D4E high altitude adaptedgene can be rapidly detected by high resolution meltingassay. Blood 2014. https://doi.org/10.1182/blood.V124.21.4875.4875.




2020     |     www.medigraphic.com