Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease.

Autor: Houweling PJ; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, Victoria, Australia., Papadimitriou ID; Institute for Health and Sport (iHeS), Victoria University, Victoria, Australia., Seto JT; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, Victoria, Australia., Pérez LM; Universidad Europea de Madrid (Faculty of Sport Sciences), Madrid, Spain.; Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain., Coso JD; Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain., North KN; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, Victoria, Australia., Lucia A; Universidad Europea de Madrid (Faculty of Sport Sciences), Madrid, Spain.; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Madrid, Spain., Eynon N; Institute for Health and Sport (iHeS), Victoria University, Victoria, Australia.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2018 Dec; Vol. 39 (12), pp. 1774-1787. Date of Electronic Publication: 2018 Nov 08.
DOI: 10.1002/humu.23663
Abstrakt: A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α-Actinin-3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint/power performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α-actinin-3 in healthy and diseased populations.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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