Angiotensin-I Converting Enzyme Genotype-Dependent Benefit from Hormone Replacement Therapy in Isometric Muscle Strength and Bone Mineral Density1
David Woods,
Gladys Onambele,
Roger Woledge,
Dawn Skelton,
Stuart Bruce,
Steve E. Humphries and
Hugh Montgomery
Department of Cardiovascular Genetics (D.W., S.E.H., H.M.), Rayne
Institute, University College London, London WC1E 6JJ, United Kingdom;
Institute of Human Performance (G.O., R.W., S.B.), University College
London, Royal National Orthapaedic Hospital, Stanmore HA7 4LP, United
Kingdom; and Department of Cellular and Integrate Biology (D.S.),
Division of Biomedical Sciences, Imperial College School of Medicine at
St. Mary’s, London W2 1PG, United Kingdom
Address all correspondence and requests for reprints to: Major David Woods, M.D., Department of Diabetes and Endocrinology, Freeman Hospital, Newcastle Upon Tyne NE7 709, United Kingdom.
Low bone mineral density (BMD) and muscle weakness are majorrisk
factors for postmenopausal osteoporotic fracture. Hormonereplacement
therapy (HRT) reverses the menopausal decline inmaximum voluntary
force of the adductor pollicis and reducesserum angiotensin-I
converting enzyme (ACE) levels. The insertion(I) allele of the ACE
gene polymorphism is associated with lowerACE activity and improved
muscle efficiency in response to physicaltraining. Therefore, we
examined whether the presence of theI allele in postmenopausal women
would affect the muscle responseto HRT. Those taking HRT showed a
significant gain in normalizedmuscle maximum voluntary force slope,
the rate of which wasstrongly influenced by ACE genotype (16.0 ±
1.53%, 14.3± 2.67%, and 7.76 ± 4.13%, mean ±
SEM forII, ID, and DD genotype, respectively;
P = 0.017 for gene effect,P =
0.004 for I allele effect). There was also a significantACE gene
effect in the response of BMD to HRT in Ward’striangle
(P = 0.03) and a significant I allele effect in the
spine(P = 0.03), but not in the neck of femur or
total hip. Thesedata suggests that low ACE activity associated with
the I alleleconfers an improved muscle and BMD response in
postmenopausalwomen treated with HRT.
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