Interaction between Angiotensin Converting Enzyme Insertion/Deletion Genotype and Exercise Training on Knee Extensor Strength in Older Individuals

Abstract

Prior data in young individuals suggest that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism interacts with exercise to affect athletic performance, but the direction of the genotype effect depends on the outcome assessed (endurance vs. strength). The purpose of this study was to determine whether the ACE I/D genotype influences physical function responses to exercise training in older individuals. Physical function (muscle strength, walking distance, and self-reported disability) was measured before and after an 18-month randomized, controlled exercise trial in 213 older (≥ 60 yrs), obese (BMI ≥ 28 kg/m2) men and women. Exercise training consisted of walking and light weight lifting for one hour 3 times/wk. At baseline, there were no associations between ACE I/D genotype and measures of physical function. Following exercise training, individuals with the DD genotype showed greater gains in knee extensor strength compared to II individuals. There was a significant (p = 0.014) interaction between ACE I/D genotype and exercise treatment on percent change in knee strength. In addition, there was a trend towards a greater improvement in physical disability score in DD genotypes (p = 0.13), but changes in 6-minute walk distance were not different between genotype groups. Thus, changes in muscle strength with exercise training in older individuals may be dependent on ACE I/D genotype.

muscle strength - ACE genotype - elderly

References

• 1 Bouchard C, Rankinen T. Individual differences in response to regular physical activity.  Med Sci Sports Exerc. 2001;  33 S446-S451
• 2 Buikema H, Pinto Y M, Rooks G, Grandjean J G, Schunkert H, van Gilst W H. The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries.  Eur Heart J. 1996;  17 787-794
• 3 Collins M, Xenophontos S L, Cariolou M A, Mokone G G, Hudson D E, Anastasiades L, Noakes T D. The ACE gene and endurance performance during the South African Ironman Triathlons.  Med Sci Sports Exerc. 2004;  36 1314-1320
• 4 Ettinger Jr W H, Burns R, Messier S P, Applegate W, Rejeski W J, Morgan T, Shumaker S, Berry M J, O'Toole M, Monu J, Craven T. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST).  JAMA. 1997;  277 25-31
• 5 Folland J, Leach B, Little T, Hawker K, Myerson S, Montgomery H, Jones D. Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload.  Exp Physiol. 2000;  85 575-579
• 6 Frederiksen H, Bathum L, Worm C, Christensen K, Puggaard L. ACE genotype and physical training effects: a randomized study among elderly Danes.  Aging Clin Exp Res. 2003;  15 284-291
• 7 Frederiksen H, Gaist D, Bathum L, Andersen K, McGue M, Vaupel J W, Christensen K. Angiotensin I-converting enzyme (ACE) gene polymorphism in relation to physical performance, cognition and survival-a follow-up study of elderly Danish twins.  Ann Epidemiol. 2003;  13 57-65
• 8 Gordon S E, Davis B S, Carlson C J, Booth F W. ANG II is required for optimal overload-induced skeletal muscle hypertrophy.  Am J Physiol. 2001;  280 E150-E159
• 9 Hernandez D, de la R A, Barragan A, Barrios Y, Salido E, Torres A, Martin B, Laynez I, Duque A, De Vera A, Lorenzo V, Gonzalez A. The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes.  J Am Coll Cardiol. 2003;  42 527-532
• 10 Jones A, Montgomery H E, Woods D R. Human performance: a role for the ACE genotype?.  Exerc Sport Sci Rev. 2002;  30 184-190
• 11 Kritchevsky S B, Nicklas B J, Visser M, Simonsick E M, Newman A B, Harris T B, Lange E M, Penninx B W, Goodpaster B H, Satterfield S, Colbert L H, Rubin S M, Pahor M. Angiotensin-converting enzyme insertion/deletion genotype, exercise, and physical decline.  JAMA. 2005;  294 691-698
• 12 Messier S P, Loeser R F, Miller G D, Morgan T M, Rejeski W J, Sevick M A, Ettinger Jr W H, Pahor M, Williamson J D. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the Arthritis, Diet, and Activity Promotion Trial.  Arthritis Rheum. 2004;  50 1501-1510
• 13 Miller G D, Rejeski W J, Williamson J D, Morgan T, Sevick M A, Loeser R F, Ettinger W H, Messier S P. The Arthritis, Diet and Activity Promotion Trial (ADAPT): design, rationale, and baseline results.  Control Clin Trials. 2003;  24 462-480
• 14 Montgomery H E, Clarkson P, Dollery C M, Prasad K, Losi M A, Hemingway H, Statters D, Jubb M, Girvain M, Varnava A, World M, Deanfield J, Talmud P, McEwan J R, McKenna W J, Humphries S. Association of angiotensin-converting-enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.  Circulation. 1997;  96 741-747
• 15 Murphey L J, Gainer J V, Vaughan D E, Brown N J. Angiotensin-converting enzyme insertion/deletion polymorphism modulates the human in vivo metabolism of bradykinin.  Circulation. 2000;  102 829-832
• 16 Myerson S, Hemingway H, Budget R, Martin J, Humphries S, Montgomery H. Human angiotensin I-converting enzyme gene and endurance performance.  J Appl Physiol. 1999;  87 1313-1316
• 17 Nelson M E, Layne J E, Bernstein M J, Nuernberger A, Castaneda C, Kaliton D, Hausdorff J, Judge J O, Buchner D M, Roubenoff R, Fiatarone Singh M A. The effects of multidimensional home-based exercise on functional performance in elderly people.  J Gerontol A Biol Sci Med Sci. 2004;  59 154-160
• 18 Nicklas B J, Ambrosius W, Messier S P, Miller G D, Penninx B W, Loeser R F, Palla S, Bleecker E, Pahor M. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial.  Am J Clin Nutr. 2004;  79 544-551
• 19 Onder G, Penninx B W, Ferrucci L, Fried L P, Guralnik J M, Pahor M. Measures of physical performance and risk for progressive and catastrophic disability: results from the Women's Health and Aging Study.  J Gerontol A Biol Sci Med Sci. 2005;  60 74-79
• 20 Rahmutula D, Nakayama T, Izumi Y, Ozawa Y, Shimabukuro H, Kawamura H, Zhen-Wang S, Xiong-Wang J, Aisa M, Run-Yang C, Mahmut M, Mahsut R, Hen-Chen Z. Angiotensin-converting enzyme gene and longevity in the Xin Jiang Uighur autonomous region of China: an association study.  J Gerontol A Biol Sci Med Sci. 2002;  57 M57-M60
• 21 Rankinen T, Wolfarth B, Simoneau J A, Maier-Lenz D, Rauramaa R, Rivera M A, Boulay M R, Chagnon Y C, Perusse L, Keul J, Bouchard C. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status.  J Appl Physiol. 2000;  88 1571-1575
• 22 Rantanen T, Guralnik J M, Foley D, Masaki K, Leveille S, Curb J D, White L. Midlife hand grip strength as a predictor of old age disability.  JAMA. 1999;  281 558-560
• 23 Rejeski W J, Ettinger Jr W H, Schumaker S, James P, Burns R, Elam J T. Assessing performance-related disability in patients with knee osteoarthritis.  Osteoarthrit Cartil. 1995;  3 157-167
• 24 Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.  J Clin Invest. 1990;  86 1343-1346
• 25 Singh M A. Exercise to prevent and treat functional disability.  Clin Geriatr Med. 2002;  18 431
• 26 Susic D, Nunez E, Frohlich E D, Prakash O. Angiotensin II increases left ventricular mass without affecting myosin isoform mRNAs.  Hypertension. 1996;  28 265-268
• 27 Thompson P D, Tsongalis G J, Ordovas J M, Seip R L, Bilbie C, Miles M, Zoeller R, Visich P, Gordon P, Angelopoulos T J, Pescatello L, Moyna N. Angiotensin-converting enzyme genotype and adherence to aerobic exercise training.  Prev Cardiol. 2006;  9 21-24
• 28 Tsianos G, Sanders J, Dhamrait S, Humphries S, Grant S, Montgomery H. The ACE gene insertion/deletion polymorphism and elite endurance swimming.  Eur J Appl Physiol. 2004;  92 360-362
• 29 Williams A G, Day S H, Folland J P, Gohlke P, Dhamrait S, Montgomery H E. Circulating angiotensin converting enzyme activity is correlated with muscle strength.  Med Sci Sports Exerc. 2005;  37 944-948
• 30 Woods D, Hickman M, Jamshidi Y, Brull D, Vassiliou V, Jones A, Humphries S, Montgomery H. Elite swimmers and the D allele of the ACE I/D polymorphism.  Hum Genet. 2001;  108 230-232
• 31 Woods D R, Montgomery H E. Angiotensin-converting enzyme and genetics at high altitude.  High Alt Med Biol. 2001;  2 201-210
• 32 Zhang B, Tanaka H, Shono N, Miura S, Kiyonaga A, Shindo M, Saku K. The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle.  Clin Genet. 2003;  63 139-144