Genetic Association of ACE Polymorphism with Sarcopenia and Effects of Genetic Regulation of ACE Activity on Muscle Function

Abstract

The purpose of this study was to investigate associations between skeletal muscle mass and ACE polymorphism, or sarcopenia‐related candidate gene, and to examine the effects of genetical angiotensin‐converting enzyme (ACE) activity on physical performance and respiratory muscle function in Korean adults. For this study, 1,464 Korean adults aged 18~79 were recruited. The anthropometrics were 1.69±0.06m (height), 63.1±5.5kg (weight), 29.4±6.5% (percent body fat), and 24.5±3.0kg/m2 (body mass index). Fat‐free mass, physical performance, gait speed (Timed Up‐and‐Go), pulmonary function (maximal inspiration and expiration pressure) and fatiguing maximum voluntary isometric contraction (40% MVIC) of ankle plantar flexor muscles with dynamic Electromyography were tested. Data of body composition and muscle functions were analyzed using one‐way ANOVA and post‐hoc Scheffe test for continuos variables and the Chi‐square test and host‐hoc Bonfferioni correction for countable variables. Blood samples for the whole blood and serum were obtained and assayed for circulating ACE activity and the ACE I/D genotype. The distribution of ACE polymorphism throughout the groups was analyzed using the Chi‐square test and host‐hoc Bonferroni correction for genetic distribution and multiple logistic regression analysis for the odds ratios (ORs) with 95% confidence intervals (CIs). We found that the distribution of ACE Indel genotype for sarcopenia was significantly different from normal population who have normal or high fat‐free mass index. Especially, we found a significantly higher (p<.05) distribution of DD genotype in sarcopenia participants (27%) than the incidence (12.5%) in normal population. The D allele of ACE genotypes in older adults indicated significantly slower gait speed than I allele of them in the Timed Up‐and‐go test (p<.05), and significantly lower levels for maximal inspiration and expiration pressure (p<.05). The II genotype in older adults indicate the highest tolerance of muscle fatigue during muscle contraction (p<.05). In conclusion, ACE Indel polymorphism and level of ACE activity is associated with sarcopenia in older adults and would genetically regulate muscle function in part. Our findings suggest that genetical concentrations of angiotensin‐converting enzyme should play a role in determining low muscle mass, slow walking speed, respiratory muscle function, and fatigue after muscle contraction in individuals. Therefore, examining ACE Indel polymorphism and ACE activity level could be used to predict sarcopenia and muscle function, and subsequently this information can be applicable to prevention and treatment to the aging muscle.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (358‐2011‐1‐G00025).