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Is there a relationship between ACTN3 R577X gene polymorphism and sarcopenia?

Abstract

Background and aims

The alpha-actinin (ACTN) genes are important structural components of the sarcomere. Sarcopenia is a common geriatric syndrome characterized by morbidity and mortality. Our study aimed to examine the relationship between the ACTN3 R577X gene and sarcopenia in community-dwelling Turkish adults.

Methods

We designed a cross-sectional study among the patients aged ≥ 65 years admitted to the geriatric outpatient clinic. We recorded the general characteristics of the patients. We used the Jamar hand dynamometer to evaluate handgrip strength. Body composition was estimated using bioimpedance analysis. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People2 criteria with population-specific cutoffs. We performed analyses of low muscle mass (LMM) with skeletal muscle mass index adjusted for body mass index [SMMI(BMI)]. We further categorized the SMMI(BMI) cutoffs into tenths. The analyzes were performed according to the 90th percentile SMMI(BMI) cutoffs. Peripheral blood samples were collected to determine the ACTN3 genotypes.

Results

197 participants were included [mean age: 76.3 ± 6.1 years, 151 (76.6%) women]. The proportions of the ACTN3 genotypes were as follows: RX (45.1%) > RR (31%) > XX (23.9%). The significant difference between genotypes was found only for low SMMI(BMI) according to the 90th percentile (p = 0.025). In multivariate analysis, only gender (female) was independently associated with LMM.

Conclusion

We did not find any association between ACTN3 R577X gene polymorphism and probable sarcopenia, confirmed sarcopenia and LMM. Besides, much more research is needed to reveal how ethnicity affects the muscles of older adults with ACTN3 R577X gene polymorphism.

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References

  1. 1.

    Bruyère O, Beaudart C, Ethgen O et al (2019) The health economics burden of sarcopenia: a systematic review. Maturitas 119:61–69. https://doi.org/10.1016/j.maturitas.2018.11.003

    Article  PubMed  Google Scholar 

  2. 2.

    Bahat G, Saka B, Erten N et al (2010) BsmI polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men. Aging Clin Exp Res 22:198–205. https://doi.org/10.1007/BF03324797

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Cruz-Jentoft AJ, Bahat G, Bauer J et al (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48:16–31. https://doi.org/10.1093/ageing/afy169 (Erratum in: Age Ageing (2019) 48:601)

    Article  PubMed  Google Scholar 

  4. 4.

    Linnemann A, van der Ven PF, Vakeel P et al (2010) The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin. Eur J Cell Biol 89:681–692. https://doi.org/10.1016/j.ejcb.2010.04.004

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Foley KS, Young PW (2014) The non-muscle functions of actinins: an update. Biochem J 459:1–13. https://doi.org/10.1042/BJ20131511

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Mills M, Yang N, Weinberger R et al (2001) Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. Hum Mol Genet 10:1335–1346. https://doi.org/10.1093/hmg/10.13.1335

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Yang N, MacArthur DG, Gulbin JP et al (2003) ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 73:627–631. https://doi.org/10.1086/377590

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Lee FX, Houweling PJ, North KN et al (2016) How does α-actinin-3 deficiency alter muscle function? Mechanistic insights into ACTN3, the “gene for speed.” Biochim Biophys Acta 1863:686–693. https://doi.org/10.1016/j.bbamcr.2016.01.013

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Del Coso J, Hiam D, Houweling P et al (2019) More than a “speed gene”: ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries. Eur J Appl Physiol 119:49–60. https://doi.org/10.1007/s00421-018-4010-0

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Cho J, Lee I, Kang H (2017) ACTN3 gene and susceptibility to sarcopenia and osteoporotic status in older Korean adults. Biomed Res Int 2017:4239648. https://doi.org/10.1155/2017/4239648

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Gunel T, Gumusoglu E, Hosseini MK et al (2014) Effect of angiotensin I-converting enzyme and α-actinin-3 gene polymorphisms on sport performance. Mol Med Rep 9:1422–1426. https://doi.org/10.3892/mmr.2014.1974

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Katz S, Downs TD, Cash HR et al (1970) Progress in development of the index of ADL. Gerontologist 10:20–30. https://doi.org/10.1093/geront/10.1_part_1.20

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186

    CAS  Article  Google Scholar 

  14. 14.

    Ravens-Sieberer U, Wille N, Badia X et al (2010) Feasibility, reliability, and validity of the EQ-5D-Y: results from a multinational study. Qual Life Res 19:887–897. https://doi.org/10.1007/s11136-010-9649-x

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Kaiser MJ, Bauer JM, Ramsch C et al (2009) Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status. J Nutr Health Aging 13:782–788. https://doi.org/10.1007/s12603-009-0214-7

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Savas S, Taşkıran E, Sarac FZ et al (2020) A cross-sectional study on sarcopenia using EWGSOP1 and EWGSOP2 criteria with regional thresholds and different adjustments in a specific geriatric outpatient clinic. Eur Geriatr Med 11:239–246. https://doi.org/10.1007/s41999-019-00256-3

    Article  PubMed  Google Scholar 

  17. 17.

    Bahat G, Cruz-Jentoft A (2019) Putting sarcopenia at the forefront of clinical practice. Eur J Geriatric Gerontol 1:43–45

    Article  Google Scholar 

  18. 18.

    Bahat G, Tufan A, Tufan F et al (2016) Cut-off points to identify sarcopenia according to European Working Group on Sarcopenia in Older People (EWGSOP) definition. Clin Nutr 35:1557–1563. https://doi.org/10.1016/j.clnu.2016.02.002

    Article  PubMed  Google Scholar 

  19. 19.

    Fess EE, Moran C (1981) Clinical assessment and recommendations, American Society of Hand Therapists. American Society of Hand Therapists, St. Louis, pp 6–8

  20. 20.

    Bahat G, Aydin CO, Tufan A et al (2021) Muscle strength cutoff values calculated from the young reference population to evaluate sarcopenia in Turkish population. Aging Clin Exp Res. https://doi.org/10.1007/s40520-021-01785-3 (Epub ahead of print)

    Article  PubMed  Google Scholar 

  21. 21.

    Kikuchi N, Yoshida S, Min SK et al (2015) The ACTN3 R577X genotype is associated with muscle function in a Japanese population. Appl Physiol Nutr Metab 40:316–322. https://doi.org/10.1139/apnm-2014-0346

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Romero-Blanco C, Artiga González MJ, Gómez-Cabello A et al (2021) ACTN3 R577X polymorphism related to sarcopenia and physical fitness in active older women. Climacteric 24:89–94. https://doi.org/10.1080/13697137.2020.1776248

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Bahat G, Tufan A, Kilic C et al (2020) Cut-off points for height, weight and body mass index adjusted bioimpedance analysis measurements of muscle mass with use of different threshold definitions. Aging Male 23:382–387. https://doi.org/10.1080/13685538.2018.1499081

    Article  PubMed  Google Scholar 

  24. 24.

    Kikuchi N, Min SK, Ueda D et al (2012) Higher frequency of the ACTN3 R allele + ACE DD genotype in Japanese elite wrestlers. J Strength Cond Res 26:3275–3280. https://doi.org/10.1519/JSC.0b013e318273679d

    Article  PubMed  Google Scholar 

  25. 25.

    Sandoval-García F, Petri MH, Saavedra MA et al (2012) The ACTN3 R577X polymorphism is associated with inflammatory myopathies in a Mexican population. Scand J Rheumatol 41:396–400. https://doi.org/10.3109/03009742.2012.669495

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Ahmetov II, Druzhevskaya AM, Lyubaeva EV et al (2011) The dependence of preferred competitive racing distance on muscle fibre type composition and ACTN3 genotype in speed skaters. Exp Physiol 96:1302–1310. https://doi.org/10.1113/expphysiol.2011.060293

    Article  PubMed  Google Scholar 

  27. 27.

    Vincent B, De Bock K, Ramaekers M et al (2007) ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics 32:58–63. https://doi.org/10.1152/physiolgenomics.00173.2007

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Santiago C, González-Freire M, Serratosa L et al (2008) ACTN3 genotype in professional soccer players. Br J Sports Med 42:71–73. https://doi.org/10.1136/bjsm.2007.039172

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Delmonico MJ, Zmuda JM, Taylor BC et al (2008) Association of the ACTN3 genotype and physical functioning with age in older adults. J Gerontol A Biol Sci Med Sci 63:1227–1234. https://doi.org/10.1093/gerona/63.11.1227

    Article  PubMed  Google Scholar 

  30. 30.

    Zempo H, Tanabe K, Murakami H et al (2010) ACTN3 polymorphism affects thigh muscle area. Int J Sports Med 31:138–142. https://doi.org/10.1055/s-0029-1242808

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Ma T, Lu D, Zhu YS et al (2018) ACTN3 genotype and physical function and frailty in an elderly Chinese population: the Rugao Longevity and Ageing Study. Age Ageing 47:416–422. https://doi.org/10.1093/ageing/afy007

    Article  PubMed  Google Scholar 

  32. 32.

    Yilmaz O, Bahat G (2017) Suggestions for assessment of muscle mass in primary care setting. Aging Male 20:168–169. https://doi.org/10.1080/13685538.2017.1311856

    Article  PubMed  Google Scholar 

  33. 33.

    Newman AB, Kupelian V, Visser M et al (2003) Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc 51:1602–1609. https://doi.org/10.1046/j.1532-5415.2003.51534.x

    Article  PubMed  Google Scholar 

  34. 34.

    Delmonico MJ, Harris TB, Lee JS et al (2007) Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women. J Am Geriatr Soc 55:769–774. https://doi.org/10.1111/j.1532-5415.2007.01140.x

    Article  PubMed  Google Scholar 

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Funding

This study was funded by the support of Istanbul University Scientific Research Projects Unit (Grant no. TSA-2019-34004). Except this, this research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Affiliations

Authors

Contributions

Concept and design: GB, MK, ASD and MAK. Carried out the studies: MK and BOT. Designed, performed and analyzed the experiments: AS, AD, SO and SP. Statistical analysis: MK, MAK and MMO. Writing original draft preparation: GB, MK and NMC. Writing review and editing: MAK, SO Supervision: MAK.

Corresponding author

Correspondence to Mustafa Kahraman.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was carried out in keeping with the principles of the Declaration of Helsinki. Approval was obtained from the Ethics Committee of Istanbul University, Istanbul Medical Faculty (No: 2018/1618). Informed consent All the participants signed an informed consent document.

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Kahraman, M., Ozulu Turkmen, B., Bahat-Ozturk, G. et al. Is there a relationship between ACTN3 R577X gene polymorphism and sarcopenia?. Aging Clin Exp Res (2021). https://doi.org/10.1007/s40520-021-01996-8

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Keywords

  • ACTN3 gene
  • Polymorphism
  • Relationship
  • Sarcopenia