The MDM2 SNP309 differentially impacts cardiorespiratory fitness in young healthy women and men.

Autor: Haddadi G; School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada., Lam B; School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada., Akhtar S; School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada., Yavelberg L; School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada., Jamnik V; School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada., Roudier E; School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada. eroudier@yorku.ca.
Jazyk: angličtina
Zdroj: European journal of applied physiology [Eur J Appl Physiol] 2024 Dec 16. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1007/s00421-024-05682-1
Abstrakt: Purpose: Maximal oxygen consumption (VO 2 max), the predominant index of cardiorespiratory fitness (CRF), is a predictor of whole-body function and longevity in humans. The central cardiac function and the skeletal muscle's capacity to use oxygen are key determinants of VO 2 max. Murine Double Minute 2 (MDM2), mainly known as an oncogene, could regulate myocardial hypertrophy, skeletal muscle angiogenesis, and oxidative phosphorylation. A prevalent single nucleotide polymorphism in the MDM2 promoter (SNP309) substitutes a T for a G, supporting a greater transcriptional activity. We aim to assess whether SNP309 impacts intrinsic CRF.
Methods: 82 young healthy nonathletic male and female adults aged 23 ± 2 years performed cardiorespiratory exercise testing to determine their VO 2 max (mL kg -1  min -1 ). The genomic DNAs isolated from saliva were genotyped using Taqman-based qPCR.
Results: A one-way ANOVA showed that SNP309 influenced relative VO 2 max in the whole cohort (p = 0.044) and in men (p = 0.009), remaining non-significant in women (p = 0.133). VO 2 max was higher in TT homozygotes than in GT heterozygotes (whole cohort, 47 ± 12 vs. 42 ± 6 mL kg -1  min -1 , p = 0.030; men, 53 ± 8 vs. 45 ± 6 mL kg -1  min -1 , p = 0.011). A contingency analysis revealed a positive association between SNP309 in men in which the TT genotype was more frequent in the high VO 2 max group (p = 0.006). When considering G as the dominant allele, men bearing a G allele had lower relative VO 2 max than TT homozygotes (47 ± 7 vs. 53 ± 8, GG/GT vs. TT, p = 0.010). Conversely, women bearing a G allele had a higher relative VO 2 max than TT homozygotes (39 ± 5 vs. 34 ± 7, GG/GT vs. TT, p = 0.047).
Conclusion: SNP309 impacts VO 2 max in a sex-dependent manner in our cohort.
Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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