Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genetics and Epigenetics

Combination of ACTN3 R577X and ACE I/D polymorphisms as a tool for prediction of obesity risk in children



The genetic influence in obesity prevalence is well described, but the role of genetic markers related to athletic strength/ endurance performance remains controversial. We investigated associations between obesity and the genetic polymorphisms alpha-actinin-3 (ACTN3) R577X and angiotensin-converting enzyme (ACE) I/D in schoolchildren aged 4–13 years from Southern Brazil. We collected sociodemographic data from parents through a questionnaire and conducted an anthropometric assessment. DNA was extracted from buccal cells and genotyping was performed by PCR. We found that 1.9% of the individuals were classified as low weight-for-age, 57.6% as normal weight and 40.5% as overweight/ obesity. Regarding allelic distribution, we found that 52.5% of individuals were DD, 30.8% ID, and 16.7% II for ACE; and 38.8% of individuals were RR, 40.2% RX and 21.0% XX for ACTN3. When both polymorphisms were combined, we observed a clear association between the composed genetic profile of these alleles and severe obesity in schoolchildren. Our data suggest that the combined analysis of ACTN3 R577X and ACE I/D polymorphisms may serve as a predictor for the risk of severe obesity in children. These data can contribute to a better understanding of the relationship between these polymorphisms and the body weight development of school-age children.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Hruby Adela, Hu FrankB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015;33:673–89.

    Article  Google Scholar 

  2. 2.

    Goodarzi MO. Series obesity 1 genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol. 2017;8587:1–14.

    Article  Google Scholar 

  3. 3.

    Hinney A, Vogel CIG, Hebebrand J. From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry. 2010;19:297–310.

    Article  Google Scholar 

  4. 4.

    Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, et al. The human obesity gene map: the 2005 update. Obesity. 2006;14:529–644.

    Article  Google Scholar 

  5. 5.

    Aranalde LCR, Pederzoli BS, Marten T, Barros FC, Basso RP, Silveira JM, et al. The ACTN3 R577X polymorphism affects the lipid profile and the prognosis of nutritional intervention in HIV-positive patients. Nutri Res. 2016;36:564–74.

    CAS  Article  Google Scholar 

  6. 6.

    Santos FG, Becker MK, Corrêa VS, Garcia DN, Vale SC, Crespo-Ribeiro JA, et al. The effect of the paraoxonase 1 (PON1) T(-107)C polymorphism on serum PON1 activity in women is dependent on fatty acid intake. Nutr Res. 2016;36:9–15.

    CAS  Article  Google Scholar 

  7. 7.

    Schadock I, Schneider A, Silva ED, Buchweitz MRD, Correa MN, Pesquero JB, et al. Simple method to genotype the ACTN3 r577x polymorphism. Genetic Testing Mol Biomarkers. 2015;19:253–7.

    CAS  Article  Google Scholar 

  8. 8.

    Mao S, Huang S. A meta-analysis of the association between angiotensin-converting enzyme insertion/ deletion gene polymorphism and the risk of overweight/obesity. J Renin-Angiotensin-Aldosterone Syst. 2015;16:687–94.

    CAS  Article  Google Scholar 

  9. 9.

    Pacholczyk M, Ferenc T, Kowalski J, Adamczyk P, Chojnowski J, Ponikowska I. Association of angiotensin-converting enzyme and angiotensin II type i receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol. 2013;32:435–42.

    CAS  Article  Google Scholar 

  10. 10.

    Kim K, Ahn N, Park J, Koh J, Jung S, Kim S, et al. Association of angiotensin-converting enzyme I/D and α-actinin-3 R577X genotypes with metabolic syndrome risk factors in Korean children. Obesity Res Clin Pract. 2016;10:S125–32.

    Article  Google Scholar 

  11. 11.

    Bienertova-Vasku J, Bienert P, Sablikova L, Slovackova L, Forejt M, Piskackova Z, et al. Effect of ID ACE gene polymorphism on dietary composition and obesity-related anthropometric parameters in the Czech adult population. Genes Nutr. 2009;4:207–13.

    CAS  Article  Google Scholar 

  12. 12.

    Lelis D, de F, Pereira AC, Krieger JE, Mill JG, Santos SHS, et al. Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population. Arch Endocrinol Metabolism. 2019;63:402–10.

    Google Scholar 

  13. 13.

    Pan YH, Wang M, Huang YM, Wang YH, Chen YL, Geng LJ, et al. ACE gene I/D polymorphism and obesity in 1,574 patients with type 2 diabetes mellitus. Dis Markers. 2016;2016:7420540.

  14. 14.

    Kim K. Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercise-mediated changes in Korean women. Eur J Appl Physiol. 2009;105:879–87.

    CAS  Article  Google Scholar 

  15. 15.

    Riedl I, Osler ME, Benziane B, Chibalin AV, Zierath JR. Association of the ACTN3 R577X polymorphism with glucose tolerance and gene expression of sarcomeric proteins in human skeletal muscle. Physiol Reports. 2015;3:1–10.

    Article  Google Scholar 

  16. 16.

    Moran CN, Yang N, Bailey MES, Tsiokanos A, Jamurtas A, MacArthur DG, et al. Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks. Eur J Human Genetics. 2007;15:88–93.

    CAS  Article  Google Scholar 

  17. 17.

    Houweling PJ, Berman YD, Turner N, Quinlan KGR, Seto JT, Yang N, et al. Exploring the relationship between α-actinin-3 deficiency and obesity in mice and humans. Int J Obesity. 2017;41:1154–7.

    CAS  Article  Google Scholar 

  18. 18.

    Ma F, Yang Y, Li X, Zhou F, Gao C, Li M, et al. The association of sport performance with ACE and ACTN3 genetic polymorphisms: a systematic review and meta-analysis. PLoS ONE. 2013;8:1–9.

    Article  Google Scholar 

  19. 19.

    Cao DY, Spivia WR, Veiras LC, Khan Z, Peng Z, Jones AE, et al. ACE overexpression in myeloid cells increases oxidative metabolism and cellular ATP. J Biol Chem. 2020;295:1369–84.

    CAS  Article  Google Scholar 

  20. 20.

    Yan X, Dvir N, Jacques M, Cavalcante L, Papadimitriou ID, Munson F, et al. ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study. J Appl Physiol. 2018;1:923–30.

    Article  Google Scholar 

  21. 21.

    Valdivieso P, Vaughan D, Laczko E, Brogioli M, Waldron S, Rittweger J, et al. The metabolic response of skeletal muscle to endurance exercise is modified by the ACE-I/D gene polymorphism and training state. Front Physiol. 2017;8:993.

Download references


This research was partially supported by CAPES, FAPERGS, and CNPq.

Author information



Corresponding author

Correspondence to Carlos Castilho Barros.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Costa, P.B., Aranalde, L.C., Correia, P.E. et al. Combination of ACTN3 R577X and ACE I/D polymorphisms as a tool for prediction of obesity risk in children. Int J Obes 45, 337–341 (2021).

Download citation


Quick links