The role of the genetic factor in the development of sarcopenia
https://doi.org/10.30629/0023-2149-2025-103-12-913-920
Abstract
Objectives. To assess the associative relationship between genotype distributions of polymorphic variants of COL1A1, VDR, NOS3, IL6, RANKL, MTHFR, MTR, MTRR genes and risk of sarcopenia in women over 60 years of age.
Materials and methods. This cross-sectional study enrolled 67 women aged 61 to 82 years. Dynamometry and a “Chair rising test” test have been performed. Polymorphic variants of the COL1A1, VDR, NOS3, IL6, RANKL, MTHFR, MTR, MTRR genes have been identified. The participants were divided into 2 groups: group 1 consisted of 34 subjects without sarcopenia and group 2 included 33 persons with sarcopenia.
Results. In group 1, the GG G894T NOS3 genotype significantly prevailed, and in group 2, the GT and TT variants were most frequent, p = 0.035. In group 1, the recessive TT genotypes G894T NOS3, GG A66G MTRR prevailed. CC variant G(-174)IL6 prevailed in group 2, as did the TT C677T MTHFR genotype, which was not detected in group 2, p < 0.05.
Conclusions. Age is an independent risk factor for sarcopenia development. Presence of the TT G894T NOS3, GG A66G MTRR genotype is likely to increase the risk of sarcopenia. While the CC G174C IL6, TT C677T MTHFR genotype is probably protective against the development of sarcopenia. There was no association between the genotype distributions of polymorphic variants of the COL1A1, VDR, RANKL, MTR genes and the risk of sarcopenia in women over 60 years of age.
About the Authors
K. S. IspavskayaRussian Federation
Ksenia S. Ispavskaya — Postgraduate student, Department of Pharmacology and Clinical Pharmacology
Yekaterinburg
N. V. Izmozherova
Russian Federation
Nadezhda V. Izmozherova — Doctor of Medical Sciences, Head, Department of Pharmacology and Clinical Pharmacology, Chief freelance specialist-clinical pharmacologist of the Ministry of health of the Sverdlovsk region
Yekaterinburg
A. A. Popov
Russian Federation
Artem A. Popov — Doctor of Medical Sciences, Head, Department of Hospital Therapy
Yekaterinburg
I. A. Pashkina
Russian Federation
Inna A. Pashkina — resident Department of Hospital Therapy
Yekaterinburg
E. V. Kudryavtseva
Russian Federation
Elena V. Kudryavtseva — Doctor of Medical Sciences, Professor, Department of Gynecology and Obstetrics
Yekaterinburg
D. L. Zornikov
Russian Federation
Danila L. Zornikov —Candidate of Medical Sciences, Docent of the Department of Medical Microbiology and Clinical Laboratory Diagnostic
Yekaterinburg
M. A. Shambatov
Russian Federation
Muraz A. Shambatov — Candidate of Medical Sciences, Associate Professor of Pharmacology and Clinical Pharmacology Chair
Yekaterinburg
V. S. Ermakov
Russian Federation
Valerii S. Ermakov — cardiac surgeon, 2 cardiac surgery department
St. Petersburg
V. N. Kravchuk
Russian Federation
Viacheslav N. Kravchuk — Doctor of Medical Sciences, Professor, Head of the Department of cardio-vascular surgical department, Professor of the first department of surgery (improvement of doctors) named after P.A. Kupriyanov Military Medical Academy after S.M. Kirov
St. Petersburg
V. V. Dalinin
Russian Federation
Vadim V. Dalinin — Doctor of Medical Sciences, Head of the Cardiosurgery Department
Moscow
References
1. Tkacheva O.N., Kotovskaya Yu.V., Runikhina N.K., Frolova E.V., Naumov A.V., Vorobyeva N.M. et al. Ostapenko V.S., Mkhitaryan E.A., Sharashkina N.V., Tyukhmenev E.A., Pereverzev A.P., Dudinskaya E.N. Clinical guidelines on frailty. Russian Journal of Geriatric Medicine. 2020;(1):11–46. (In Russian). DOI: 10.37586/2686-8636-1-2020-11-46
2. Cruz-Jentoft A.J., Bahat, G., Bauer J., Boirie Y., Bruyère O., Cederholm T. et al., Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2 (2019). Sarcopenia: revised European consensus on definition and diagnosis. Age and ageing. 2019;48(1):16–31. DOI: 10.1093/ageing/afy169
3. Bocharova KA, Rukavishnikova SA, Osipov KV, et al. Sarcopenia in the longterm care system. Current Problems of Health Care and Medical Statistics. 2021;2:12–26 (In Russian). DOI:10.24412/2312-2935-2021-2-12-26
4. Gomes M.J., Martinez P.F., Pagan L.U., Damatto R.L., Cezar M.D.M., Lima A.R.R., Okoshi K., Okoshi M.P. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget. 2017;8 (12):20428–40. DOI: 10.18632/onco-target.14670
5. Melouane A., Ghanemi A., Yoshioka M., St-Amand J. Functional genomics applications and therapeutic implications in sarcopenia. Mutation Researh. 2019;781:175–85. DOI: 10.1016/j.mrrev.2019.04.003
6. Sgrò P., Sansone M., Sansone A., Sabatini S., Borrione P., Romanelli F., Di Luigi L. Physical exercise, nutrition and hormones: three pillars to fight sarcopenia. The aging male: the official journal of the International Society for the Study of the Aging Male, 2019;22(2):75– 88. DOI: 10.1080/13685538.2018.1439004
7. Khanal P., He L., Stebbings G., Onambele-Pearson G.L., Degens H., Williams A., Thomis M., Morse C.I. Prevalence and association of single nucleotide polymorphisms with sarcopenia in older women depends on definition. Scientific reports. 2020;19;10(1):2913. doi: 10.1038/s41598-020-59722-9
8. Verkhoturova S.V., Tsarenok S.U., Gorbunov V.V., Aksenova T.A. Polymorphism of some genes of bone tissue metabolism (VDR Bsm1 c.IVS7G>A, LCT 13910 T>C, COL1A 12046 G->T) among the representatives of Russian and Buryat nationalities. Osteoporosis and Bone Diseases. 2017;20(1):3–6. (In Russian). DOI: 10.14341/osteo201713-6
9. GWAS Catalog — EMBL-EBI. [Электронный ресурс] URL: https://www.ebi.ac.uk/gwas/ (дата обращения — ноябрь 2019 г.)
10. DisGeNET Database 6.0. [Электронный ресурс] URL: https://www.disgenet.org/ (дата обращения — январь 2020 г.).
11. McConell G.K., Rattigan S., Lee-Young R.S., Wadley G.D., Merry T.L. Skeletal muscle nitric oxide signaling and exercise: a focus on glucose metabolism. American journal of physiology. Endocrinology and metabolism, 2012;303(3):E301–E307. DOI: 10.1152/ajpendo.00667.2011
12. Zmijewski P., Cięszczyk P., Ahmetov I.I., Gronek P., LulińskaKuklik E., Dornowski M. et al. The NOS3 G894T (rs1799983) and -786T/C (rs2070744) polymorphisms are associated with elite swimmer status. Biology of sport. 2018;35(4)”313–319. DOI: 10.5114/biolsport.2018.76528
13. Weyerstraß J., Stewart K., Wesselius A., Zeegers M. Nine genetic polymorphisms associated with power athlete status — A MetaAnalysis. Journal of science and medicine in sport. 2018;21(2):213– 220. DOI: 10.1016/j.jsams.2017.06.012
14. Ferrari S.L., Ahn-Luong L., Garnero P., Humphries S.E., Greenspan S.L. Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. The Journal of clinical endocrinology and metabolism, 2003;88(1):255–259. DOI: 10.1210/jc.2002-020092
15. Serrano A.L., Baeza-Raja B., Perdiguero E., Jardí M., MuñozCánoves P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell metabolism, 2008;7(1):33–44. DOI: 10.1016/j.cmet.2007.11.011
16. Salminen A., Huuskonen J., Ojala J., Kauppinen A., Kaarniranta K., Suuronen T. Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing research reviews. 2008;7(2):83–105. DOI: 10.1016/j.arr.2007.09.002
17. Kovalev V.V., Kudryavtseva E.V., Milyaeva N.M. Belomestnov S.R. Great obstetric syndromes: “gordian knot” of genetic networks. Ural Medical Journal. 2018;13(168):40–47. (In Russian). DOI 10.25694/URMJ.2018.13.45
18. De Giuseppe R., Tomasinell, C.E., Vincenti A., Di Napoli I., Negro M., & Cena H. Sarcopenia and homocysteine: is there a possible association in the elderly? A narrative review. Nutrition research reviews. 2022;35(1):98–111. DOI: 10.1017/S095442242100010X
19. Urzi F, Pokorny B, Buzan E. Pilot Study on Genetic Associations With Age-Related Sarcopenia. Frontiers in genetics. 2021;11:615238. DOI: 10.3389/fgene.2020.615238
20. Khanal P., Williams A.G., He L. et al. Sarcopenia, obesity, and sarcopenic obesity: relationship with skeletal muscle phenotypes and single nucleotide polymorphisms. Journal of clinical medicine. 2021;10(21):4933. DOI: 10.3390/jcm10214933
21. Zarebska A., Ahmetov I.I., Sawczyn S., Weiner A.S., Kaczmarczyk M., Ficek K.et al. Association of the MTHFR 1298A>C (rs1801131) polymorphism with speed and strength sports in Russian and Polish athletes. Journal of sports sciences. 2014;32(4):375–382. DOI: 10.1080/02640414.2013.825731
22. Kokh N.V., Slepukhina A.A., Lifshits G.I. Folate cycle: review and practical recommendations for the interpretation of genetic tests. Medical Genetics. 2015;14(11):3–8. (In Russian). DOI: 10.1234/XXXXXXXX-2015-11-3-8
23. Li W.X., Cheng F., Zhang A.J., Dai S.X., Li G.H., Lv W.W. et al. Folate deficiency and gene polymorphisms of MTHFR, MTR and MTRR elevate the hyperhomocysteinemia risk. Clinical laboratory.2017;63(3):523–533. DOI: 10.7754/Clin.Lab.2016.160917
24. Walsh S., Ludlow A.T., Metter E.J., Ferrucci L., Roth S.M. Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia. Aging Clinical and Experimental Research. 2016;28 (3):435–42. DOI: 10.1007/s40520-015-0447-8
25. Kudryavtseva E.V., Berezina D.A., Kornilov D.O., Simarzina V.M., Tryapitsyn M.A., Bekhter A.A., Kovalev V.V., Zornikov D.L. Some molecular genetic determinants of premature aging of women. Consilium Medicum. 2024;26(12):809– 814. (In Russian). DOI: 10.26442/20751753.2024.12.20297
26. Yao X., Yang L., Li M., Xiao H. Relationship of vitamin D receptor gene polymorphism with sarcopenia and muscle traits based on propensity score matching. Journal of clinical laboratory analysis. 2020; 4(11):e23485. DOI: 10.1002/jcla.23485
27. Garatachea N., Lucía A. Genes and the ageing muscle: a review on genetic association studies. Age (Dordrecht, Netherlands). 2013;35(1):207–233. DOI: 10.1007/s11357-011-9327-0
28. Karasik D., Zhou Y., Cupples,L.A., Hannan M.., Kiel, D.P., Demissie S. Bivariate genome-wide linkage analysis of femoral bone traits and leg lean mass: Framingham study. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2009;24(4):710–718. DOI: 10.1359/jbmr.081222
29. Khanal P., He L., Herbert A.J., Stebbings G.K., OnambelePearson G.L., Degens H. et al. The association of multiple gene variants with ageing skeletal muscle phenotypes in elderly women. Genes (Basel). 2020;11(12):1459. DOI: 10.3390/genes11121459
30. Kucher A.N. Molecular and genetic markers of sarkopenia. Molekulyarnaya meditsina. 2021;19(1):17–29 (In Russian). DOI: 10.29296/24999490-2021-01-03
Review
For citations:
Ispavskaya K.S., Izmozherova N.V., Popov A.A., Pashkina I.A., Kudryavtseva E.V., Zornikov D.L., Shambatov M.A., Ermakov V.S., Kravchuk V.N., Dalinin V.V. The role of the genetic factor in the development of sarcopenia. Clinical Medicine (Russian Journal). 2025;103(12):913-920. (In Russ.) https://doi.org/10.30629/0023-2149-2025-103-12-913-920
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