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Published ahead of print on April 29, 2004, doi:10.1164/rccm.200304-578OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 4, August 2004, 395-399

A more recent version of this article appeared on August 15, 2004
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Submitted on April 27, 2003
Accepted on April 23, 2004

Angiotensin Converting Enzyme Genotype and Strength in Chronic Obstructive Pulmonary Disease

Nicholas S Hopkinson1*, Annabel H Nickol1, John Payne2, Emma Hawe2, William D-C Man3, John Moxham3, Hugh Montgomery2, and Michael I Polkey1

1 Respiratory Muscle Laboratory, Royal Brompton Hospital, London, United Kingdom, 2 Department of Cardiovascular Genetics, Rayne Institute, London, United Kingdom, 3 Respiratory Muscle Laboratory, King's College Hospital, Guy's King's and St. Thomas' School of Medicine, London, United Kingdom

* To whom correspondence should be addressed. E-mail: n.hopkinson{at}ic.ac.uk.

Quadriceps muscle weakness is an important contributor to exercise limitation in patients with chronic obstructive pulmonary disease. The deletion allele of the angiotensin converting enzyme gene polymorphism has previously been associated with a greater response to strength training in healthy subjects and might therefore protect against detraining in these patients. In 103 stable outpatients (mean FEV1 34.4(16.5)% predicted) the deletion allele was associated with greater isometric quadriceps strength; mean(SD) 31.4(10.8) Kg for insertion homozygotes, 34.1(13.0) Kg for heterozygotes and 38.3(11.6) Kg for deletion homozygotes (p=0.04 linear trend). Adjusted for fat free mass the relationship was stronger (linear trend p=0.007). There was no relationship between strength and genotype in a group of 101 age-matched healthy controls. Twitch quadriceps force in response to magnetic femoral nerve stimulation, measured in 39 patients was also genotype dependent; 8.3(2.6) Kg for insertion homozygotes, 10.1(3.6) Kg for heterozygotes and 12.4(3.5) Kg for deletion homozygotes (p=0.002 linear trend). Body mass index and fat free mass did not differ significantly between genotypes in either group. There was no association in either patients or controls between genotype and inspiratory muscle strength. In chronic obstructive pulmonary disease the deletion allele is associated with greater quadriceps strength independent of confounding factors.
Key words: Gene polymorphism, skeletal muscle, respiratory muscle




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