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Angiotensin Converting Enzyme Genotype and Strength in Chronic Obstructive Pulmonary Disease

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

Correspondence and requests for reprints should be addressed to Nicholas Hopkinson, M.A., M.R.C.P., Respiratory Muscle Laboratory, Royal Brompton Hospital, Fulham Road, London, SW3 6NP, United Kingdom. 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 [SD] FEV₁ 34.4 [16.5] % predicted), the angiotensin 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 correlation between strength and genotype in a group of 101 age-matched healthy control subjects. 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 control subjects 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 • respiratory muscle • skeletal muscle

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