The ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status

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dc.authorid0000-0003-4026-9883
dc.authorid0000-0001-5157-7430
dc.authorid0000-0002-6314-4883
dc.authorid0000-0002-3014-2005
dc.authorid0000-0002-6335-4020
dc.authorid0009-0006-8904-9493
dc.contributor.authorCigirtas, Rukiye
dc.contributor.authorBulgay, Celal
dc.contributor.authorKazan, Hasan Hueseyin
dc.contributor.authorAkman, Onur
dc.contributor.authorSporis, Goran
dc.contributor.authorJohn, George
dc.contributor.authorAhmetov, Ildus I.
dc.date.accessioned2026-02-28T12:18:16Z
dc.date.available2026-02-28T12:18:16Z
dc.date.issued2024
dc.departmentBayburt Üniversitesi
dc.description.abstractBackground: Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle fiber size, contraction force, and exercise capacity, along with defects in calcium handling within fast-twitch muscle fibers. However, the role of the ARK2N gene in human muscle physiology, and particularly in athletic populations, remains poorly understood. The aim of this study was threefold: (a) to compare ARK2N gene expression between power and endurance athletes; (b) to analyze the relationship between ARK2N gene expression and muscle fiber composition; and (c) to investigate the association between the functional variant of the ARK2N gene, muscle fiber size, and sport-related phenotypes. Results: We found that ARK2N gene expression was significantly higher in power athletes compared to endurance athletes (p = 0.042) and was positively associated with the proportion of oxidative fast-twitch (type IIA) muscle fibers in untrained subjects (p = 0.017, adjusted for age and sex). Additionally, we observed that the ARK2N rs6507691 T allele, which predicts high ARK2N gene expression (p = 3.8 x 10-12), was associated with a greater cross-sectional area of fast-twitch muscle fibers in strength athletes (p = 0.015) and was over-represented in world-class strength athletes (38.6%; OR = 2.2, p = 0.023) and wrestlers (33.8%; OR = 1.8, p = 0.044) compared to controls (22.0%). Conclusions: In conclusion, ARK2N appears to be a gene specific to oxidative fast-twitch myofibers, with its functional variant being associated with muscle fiber size and strength-athlete status.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK); Scientific and Technological Research Council of Trkiye; Russian Science Foundation [24-15-00413]; [2209-A]
dc.description.sponsorshipThe Turkish part of the study was supported by The Scientific and Technological Research Council of Turkiye (TUBITAK; 2209-A). The Russian part of the study (muscle biopsy, gene-expression analyses, and genotyping) was supported by a grant from the Russian Science Foundation (grant no. 24-15-00413: 'Evaluation of environmental and molecular genetic factors influencing long-term and short-term changes in human skeletal muscle fibre phenotype and body composition with regard to physical activity parameters').
dc.identifier.doi10.3390/metabo14120684
dc.identifier.issn2218-1989
dc.identifier.issue12
dc.identifier.pmid39728465
dc.identifier.scopus2-s2.0-85213301441
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.3390/metabo14120684
dc.identifier.urihttps://hdl.handle.net/20.500.12403/6196
dc.identifier.volume14
dc.identifier.wosWOS:001384621400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofMetabolites
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260218
dc.subjectpolymorphism
dc.subjectgenotype
dc.subjectgene expression
dc.subjectSNP
dc.subjectathlete status
dc.subjectweightlifting
dc.subjectsport
dc.subjectmolecular physiology
dc.subjectmuscle hypertrophy
dc.subjectskeletal muscle
dc.titleThe ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status
dc.typeArticle

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