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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 572, (2004)
© 2004 American Thoracic Society


Correspondence

ACE Gene Polymorphism in COPD

To the Editor:

The study of Hopkinson and colleagues (1) showed that in patients with chronic obstructive pulmonary disease (COPD) the deletion allele (D) of the ACE polymorphism was associated with greater quadriceps strength compared with the insertion allele (I), and the authors suggested that this may also apply for exercise capacity. This is remarkable, because in healthy subjects it has consistently been reported that I, but not D, is positively associated with enhanced exercise and muscle performance (2).

We have evaluated the ACE gene polymorphism, determined by polymerase chain reaction (3), in 95 patients with COPD (65 males and 30 females, aged 65 years, FEV1 39% of predicted) submitted to an 8-week pulmonary rehabilitation program comprising five exercise training sessions per week. ACE genotype distribution was comparable with that described by Hopkinson and colleagues (DD 32%; ID 50%; II 19%). Exercise capacity, measured by means of the maximal work load achieved during exhaustive incremental cycle ergometry (Wmax), was similar for all ACE genotypes at baseline (DD 57.5 W; II/ID 52.3 W), but I, and not D, was associated with an enhanced response to physical training (DD 6.0 ± 9.8 W; II/ID 14.4 ± 12 W; mean ± SD; p = 0.04).

It thus seems that exercise capacity, in contrast to muscle strength, is not associated with D in COPD. One could speculate that I is associated with enhanced improvement and/or preservation of endurance and D with better improvement and/or preservation of muscle strength. Unfortunately, in our study quadriceps strength was not measured. As in the study by Hopkinson and coworkers, no baseline association between ACE genotype and fat-free mass was found. However, this does not exclude the possibility that muscular properties other than variations in muscle mass are responsible for differences in muscle function. For example, I has been associated with increased proportions of fatigue-resistant slow-twitch fibers—and thus with decreased fast-twitch fiber proportions—in healthy subjects (4). In addition, impaired peripheral tissue oxygenation has been associated with D in COPD (5). It can therefore be hypothesized that a higher proportion of fast-twitch fibers underlies the D allele–associated preservation of muscle strength in the study by Hopkinson and colleagues, whereas in our study the I allele–associated increase in Wmax might be due to a higher proportion of slow-twitch fibers and/or better muscle oxygenation. To resolve this hypothesis, it is important that in future studies assessment of both muscle strength and endurance are included, in combination with muscle biopsy analysis of fiber types.

Harry R. Gosker, Herman-Jan Pennings and Annemie M. W. J. Schols

Maastricht University Maastricht, The Netherlands

FOOTNOTES

Conflict of Interest Statement: H.R.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter; H.-J.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter; A.M.W.J.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter.

REFERENCES

  1. Hopkinson NS, Nickol AH, Payne J, Hawe E, Man WD, Moxham J, Montgomery H, Polkey MI. Angiotensin converting enzyme genotype and strength in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:395–399.[Abstract/Free Full Text]
  2. Williams AG, Rayson MP, Jubb M, World M, Woods DR, Hayward M, Martin J, Humphries SE, Montgomery HE. The ACE gene and muscle performance. Nature 2000;403:614.[Medline]
  3. van Suylen RJ, Wouters EF, Pennings HJ, Cheriex EC, van Pol PE, Ambergen AW, Vermelis AM, Daemen MJ. The DD genotype of the angiotensin converting enzyme gene is negatively associated with right ventricular hypertrophy in male patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1791–1795.[Abstract/Free Full Text]
  4. 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.[CrossRef][Medline]
  5. Kanazawa H, Otsuka T, Hirata K, Yoshikawa J. Association between the angiotensin-converting enzyme gene polymorphisms and tissue oxygenation during exercise in patients with COPD. Chest 2002;121:697–701.[Abstract/Free Full Text]



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