<I>ACTN3</I> R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude

Ricardo Muller Bottura; Giscard Humberto Oliveira Lima; Debora Cristina Hipolide; Joao Bosco Pesquero

doi:doi:10.11648/j.ijgg.20200804.14

| Peer-Reviewed

ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude

Ricardo Muller Bottura, Giscard Humberto Oliveira Lima, Debora Cristina Hipolide, Joao Bosco Pesquero

Published in International Journal of Genetics and Genomics (Volume 8, Issue 4)

Received: 26 October 2020 Accepted: 10 November 2020 Published: 23 November 2020

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO₂ and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.

Published in	International Journal of Genetics and Genomics (Volume 8, Issue 4)
DOI	10.11648/j.ijgg.20200804.14
Page(s)	138-142
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

ACTN3, Glycemia, Hypoxia, Hypoxemia, Muscle Fiber Type

References

[1]	Antonio J, Knafo S, Ellerbroek A, Vargas L, Silver T, Peacock C, Tartar J (2017). The Relationship between the ACTN3 Genotype and Measures of Stress, Exercise Performance and Body Composition: A Pilot Trial. Journal of Exercise. Dec; 20 (6): 139-53.
[2]	Aranalde LC, Pederzoli BS, Marten T, Barros FC, Basso RP, Silveira JM, Valle SC, Pieniz S, Araujo RC, Paredes-Gamero EJ, Schadock I, Schneider A, Barros CC (2016). The ACTN3 R577X polymorphism affects the lipid profile and the prognosis of nutritional intervention in HIV-positive patients. Nutr Res. Jun; 36 (6): 564-74.
[3]	Baldari C, Bonavolontà V, Emerenziani GP, Gallotta MC, Silva AJ, and Guidetti L (2009). Accuracy, reliability, linearity of Accutrend and Lactate Pro versus EBIO plus analyzer. Eur J Appl Physiol. 107 (1): 105-111.
[4]	Bottura RM, Lima GHO, Hipolide DC, Pesquero JB (2019). Association between ACTN3 and acute mountain sickness. Genes Environ. Dec 10; 41: 18.
[5]	Brooks GA, Butterfield GE, Wolfe RR, Groves BM, Mazzeo RS, Sutton JR, Wolfel EE, and Reeves JT (1991). Increased dependence on blood glucose after acclimatization to 4,300 m. J Appl Physiol. 70 (2): 919-927.
[6]	Brooks GA, Wolfel EE, Groves BM, Bender PR, Butterfield GE, Cymerman A, Mazzeo RS, Sutton JR, Wolfe RR, and Reeves JT (1992). Muscle accounts for glucose disposal but not blood lactate appearance during exercise after acclimatization to 4,300 m. J Appl Physiol. 72 (6): 2435-2445.
[7]	Chen SM, Lin HY, Kuo CH (2015). Altitude training improves glycemic control. Chin J Physiol. 56 (4): 193-8.
[8]	Conlee RK, Rennie MJ, Winder WW (1976). Skeletal muscle glycogen content: diurnal variation and effects of fasting. Am J Physiol. Aug; 231 (2): 614-18.
[9]	Desjardins P, and Conklin D (2010). NanoDrop microvolume quantitation of nucleic acids. J Vis Exp. 22 (45): 2565.
[10]	Ge RL, Simonson TS, Gordeuk V, Prchal JT, and McClain DA (2015). Metabolic aspects of high-altitude adaptation in Tibetans. Exp Physiol. 100 (11): 1247-1255.
[11]	Gilbert-Kawai ET, Milledge JS, Grocott MP, and Martin DS (2014). King of the mountains: Tibetan and Sherpa physiological adaptations for life at high altitude. Physiology (Bethesda). 29 (6): 388-402.
[12]	Hill NE, Deighton K, Matu J, Misra S, Oliver NS, Newman C, Mellor A, O'Hara J, Woods D (2018). Continuous Glucose Monitoring at High Altitude-Effects on Glucose Homeostasis. Med Sci Sports Exerc. Aug; 50 (8): 1679-1686.
[13]	Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH, Howard DJ, Fernandez BO, Burgess SL, Ament Z, Gilbert-Kawai ET, Vercueil A, Landis BD, Mitchell K, Mythen MG, Branco C, Johnson RS, Feelisch M, Montgomery HE, Griffin JL, Grocott MPW, Gnaiger E, Martin DS, Murray AJ (2017). Metabolic basis to Sherpa altitude adaptation. Proc Natl Acad Sci U S A. Jun 13; 114 (24): 6382-6387.
[14]	Iyriboz Y, Powers S, Morrow J, Ayers D, and Landry G (1991). Accuracy of pulse oximeters in estimating heart rate at rest and during exercise. Br J Sports Med. 25 (3): 162-164.
[15]	Khani S, Tayek JA (2001). Cortisol increases gluconeogenesis in humans: its role in the metabolic syndrome. Clin Sci (Lond). Dec; 101 (6): 739-47.
[16]	Kelly KR, Williamson DL, Fealy CE, Kriz DA, Krishnan RK, Huang H, Ahn J, Loomis JL, and Kirwan JP (2010). Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy humans. Metabolism. 59 (2): 200–205.
[17]	Koufakis T, Karras SN, Mustafa OG, Zebekakis P, Kotsa K (2019). The Effects of High Altitude on Glucose Homeostasis, Metabolic Control, and Other Diabetes-Related Parameters: From Animal Studies to Real Life. High Alt Med Biol. Mar; 20 (1): 1-11.
[18]	Lipsitz LA, Hashimoto F, Lubowsky LP, Mietus J, Moody GB, Appenzeller O, and Goldberger AL (1995). Heart rate and respiratory rhythm dynamics on ascent to high altitude. Br Heart J. 74 (4): 390-396.
[19]	Litch JA (1996). Drug-induced hypoglycemia presenting as acute mountain sickness, after mistaking acetohexamide for acetazolamide. Wilderness Environ Med. 7 (3): 232-5.
[20]	North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, and Beggs AH (1999). A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nat Genet. 21 (4): 353-354.
[21]	Quinlan KG, Seto JT, Turner N, Vandebrouck A, Floetenmeyer M, Macarthur DG, Raftery JM, Lek M, Yang N, Parton RG, Cooney GJ, North KN (2010). Alpha-actinin-3 deficiency results in reduced glycogen phosphorylase activity and altered calcium handling in skeletal muscle. Hum Mol Genet. Apr 1; 19 (7): 1335-46.
[22]	Roach RC, Maes D, Sandoval D, Robergs RA, Icenogle M, Hinghofer-Szalkay H, Lium D, Loeppky JA (2000). Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol. 88 (2): 581-5.
[23]	Roach RC, Hackett PH, Oelz O, Bärtsch P, Lucks AM, MacInnis MJ, Bailie JK, and The Lake Louise AMS Score Consensus Committee (2018). The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol. 19 (1): 4-6.
[24]	Schadock I, Schneider A, Silva ED, Buchweitz MR, Correa MN, Pesquero JB, Paredes-Gamero EJ, Araujo RC, Barros CC (2015). Simple Method to Genotype the ACTN3 r577x Polymorphism. Genet Test Mel Biomarkers. 19 (5): 253-257.
[25]	Vincent B, De Bock K, Ramaekers M, den Eede EV, Van Leemputte M, Hespel P, and Thomis MA (2007). ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics. 32: 58-63.
[26]	Woods DR, Davison A, Stacey M, Smith C, Hooper T, Neely D, Turner S, Peaston R, Mellor A (2012). The cortisol response to hypobaric hypoxia at rest and post-exercise. Horm Metab Res. Apr; 44 (4): 302-5.

Cite This Article

Plain Text BibTeX RIS

APA Style

Ricardo Muller Bottura, Giscard Humberto Oliveira Lima, Debora Cristina Hipolide, Joao Bosco Pesquero. (2020). ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude. International Journal of Genetics and Genomics, 8(4), 138-142. https://doi.org/10.11648/j.ijgg.20200804.14

Copy | Download

ACS Style

Ricardo Muller Bottura; Giscard Humberto Oliveira Lima; Debora Cristina Hipolide; Joao Bosco Pesquero. ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude. Int. J. Genet. Genomics 2020, 8(4), 138-142. doi: 10.11648/j.ijgg.20200804.14

Copy | Download

AMA Style

Ricardo Muller Bottura, Giscard Humberto Oliveira Lima, Debora Cristina Hipolide, Joao Bosco Pesquero. ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude. Int J Genet Genomics. 2020;8(4):138-142. doi: 10.11648/j.ijgg.20200804.14

Copy | Download

@article{10.11648/j.ijgg.20200804.14,
  author = {Ricardo Muller Bottura and Giscard Humberto Oliveira Lima and Debora Cristina Hipolide and Joao Bosco Pesquero},
  title = {ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude},
  journal = {International Journal of Genetics and Genomics},
  volume = {8},
  number = {4},
  pages = {138-142},
  doi = {10.11648/j.ijgg.20200804.14},
  url = {https://doi.org/10.11648/j.ijgg.20200804.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20200804.14},
  abstract = {Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2 and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.},
 year = {2020}
}

Copy | Download

TY  - JOUR
T1  - ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude
AU  - Ricardo Muller Bottura
AU  - Giscard Humberto Oliveira Lima
AU  - Debora Cristina Hipolide
AU  - Joao Bosco Pesquero
Y1  - 2020/11/23
PY  - 2020
N1  - https://doi.org/10.11648/j.ijgg.20200804.14
DO  - 10.11648/j.ijgg.20200804.14
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 138
EP  - 142
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20200804.14
AB  - Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2 and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.
VL  - 8
IS  - 4
ER  -

Copy | Download

Author Information

Ricardo Muller Bottura

Psychobiology Department, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
Giscard Humberto Oliveira Lima

Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italia
Debora Cristina Hipolide

Psychobiology Department, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
Joao Bosco Pesquero

Biophysics Department, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Ricardo Muller Bottura, Giscard Humberto Oliveira Lima, Debora Cristina Hipolide, Joao Bosco Pesquero. (2020). ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude. International Journal of Genetics and Genomics, 8(4), 138-142. https://doi.org/10.11648/j.ijgg.20200804.14

Copy | Download

ACS Style

Ricardo Muller Bottura; Giscard Humberto Oliveira Lima; Debora Cristina Hipolide; Joao Bosco Pesquero. ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude. Int. J. Genet. Genomics 2020, 8(4), 138-142. doi: 10.11648/j.ijgg.20200804.14

Copy | Download

AMA Style

Ricardo Muller Bottura, Giscard Humberto Oliveira Lima, Debora Cristina Hipolide, Joao Bosco Pesquero. ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude. Int J Genet Genomics. 2020;8(4):138-142. doi: 10.11648/j.ijgg.20200804.14

Copy | Download

@article{10.11648/j.ijgg.20200804.14,
  author = {Ricardo Muller Bottura and Giscard Humberto Oliveira Lima and Debora Cristina Hipolide and Joao Bosco Pesquero},
  title = {ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude},
  journal = {International Journal of Genetics and Genomics},
  volume = {8},
  number = {4},
  pages = {138-142},
  doi = {10.11648/j.ijgg.20200804.14},
  url = {https://doi.org/10.11648/j.ijgg.20200804.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20200804.14},
  abstract = {Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2 and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.},
 year = {2020}
}

Copy | Download

TY  - JOUR
T1  - ACTN3 R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude
AU  - Ricardo Muller Bottura
AU  - Giscard Humberto Oliveira Lima
AU  - Debora Cristina Hipolide
AU  - Joao Bosco Pesquero
Y1  - 2020/11/23
PY  - 2020
N1  - https://doi.org/10.11648/j.ijgg.20200804.14
DO  - 10.11648/j.ijgg.20200804.14
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 138
EP  - 142
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20200804.14
AB  - Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2 and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.
VL  - 8
IS  - 4
ER  -

Copy | Download