This study has significance in that it is the first study to show a relationship between the ACE activity across the ACE genotypes and muscle endurance by quantify muscle fatigability, objectively, using a dynamic EMG in the elderly of the same age.
In addition, this is the comprehensive study to analyze the difference of the muscular function and body composition, according to the ACE activity, as well as the ACE genotype.
Although, the frequencies of the ACE ID alleles vary considerably in the midst of different races, recent previous studies had reported that it was ID, II, and DD, in order. In the present study, the frequencies for II, ID and DD genotypes of the ACE gene were 30.6%, 44.9% and 24.5%, respectively, and thus, ID type is the most common, followed by II and DD type in Korean population. This finding was not different from the previously reported studies. As compared according to the sex, the frequencies for II, ID and DD genotypes were ID 43.5%, II 30.4%, and DD 26.1% in men, and were ID 46.1%, II 30.7%, and DD 23.1% in women, as the same order ().
In this study, the ACE activity and handgrip strength did not have significant association, but the ACE activity and endurance time, as well as the mean frequency change showed a statistic association, regardless of the sex.
In addition, since the ACE activity differs according to the ACE genotype, we try to find out whether the muscular strength and muscular endurance are different according to the different ACE genotypes.
Grip strength, as an indicator of muscle strength, was not significantly different across the three genotype groups in both genders.
As an indicator of muscle endurance, endurance time was significantly longer, and the mean frequency change was less in II genotype than that of DD genotype, analyzed separated by men and women.
In the gender division, there were same results on the male subject group, as the analysis of the whole group. But it showed only the tendency on the comparison of average value on the female subject group (). In conclusion, the II type showed a lower ACE activity than the DD type, and it had similar muscle strength. But II type showed superior muscle endurance than DD type.
In II genotypes, the muscle strength was not significantly different, but the muscle endurance was significantly superior and ACE activity was lower, in comparison to the DD genotypes.
Previous epidemiologic studies pointed out that the presence of the I allele gives rise to lower the ACE activity in the serum, whereas, those individuals with the DD allele typically have higher circulating and endogenous ACE levels.24
This trend remains significant across the three genotype groups in this study, as well.
In the present study, only the upper limb muscle strength was measured, using a handgrip dynamometry. Handgrip dynamometer had been used as a precise and consistent method for the measurement of one's muscle strength.
However, because the previous studies had shown strong and significant correlations and similar pattern of the muscle strength loss between the upper and lower limbs, it can be used as a surrogate to generalize the muscle function of the whole body.5
We have concluded that no clear association was observed between the muscle strength and ACE genotypes or activity, as to several previous studies.25
However, the other previous investigators had suggested that DD genotype with higher ACE activity have greater strength/power at high velocities than II, ID genotypes,24
because the D allele stimulates the skeletal muscle hypertrophy.4
A possible explanation for that discrepancy may be related to the bias, which is derived from many factors, such as the duration and velocity of contraction, the thickness of subcutaneous tissue, muscle length and fiber-type, gender, age, motor recruitment, neurological, endogenous and psychological events.
In this study, muscle endurance was estimated that measured the duration time of the muscle contraction and muscle fatigue, upon the ACE genotype like the previous study.27
Failure to maintain the required or expected force, defined as muscle fatigue,29
is accompanied by the shift toward the lower frequencies of the surface myoelectric signal power spectrum.13
The lower EMG power spectrum shift, during fatigue, is considered to be related to the biochemical by-product accumulation (H+ and lactic acid) in the muscle, which changes the potential conduction velocity, increased firing rate, and/or synchronization of motor, and additional recruitment of motor units.
The build-up of lactic acid during glycolysis in muscle contraction contributes to the delayed repolarization period, and thus, the refractory period is longer. Conduction velocity of action potential and change of the mean frequency decreases, as the inter-depolarization interval increases. Overall, the changes in motor unit conduction velocity, firing rate, recruitment, and synchronization may jointly interact to frequency shift of the power spectrum toward lower frequencies as fatigue progresses. Further, the degree of frequency shift is influenced by the muscle properties, duration and strength of contraction.13
By the way, in muscles with a high proportion of fast-twitch (type II) fibers being more fatigable, the mean frequency change will be greater, as more lactic acid is accumulated.30
As muscle fatigue was measured with the rate of change in the mean frequency, according to time and the mean frequency slope (change/min) in the previous study,31
our study tried to estimate the muscle fatigue by a change in the mean frequency for 20 seconds of the beginning and end of submaximal voluntary contraction for 2 minutes. This study needed to set up the section for measuring the change within the same contraction time, and minimum value of the recorded endurance time was 121 seconds. Therefore, we decided 2 minutes by section.
The electromyographic parameter obtained, using surface EMG, can differ from position of electrode and individual characteristics, like subcutaneous fat or muscle condition. Therefore, MVC was measured for marking the relative electromyographic value.13
In addition, this value was considered as the maximum activity of electromyelography gained by spontaneous maximum muscle contraction.21
It was measured as the duration time of the muscle contraction by calculating 40% MVC.
In the previous studies concerning the isometric muscle contraction, MVC target level was various as 15-80%,33
but in the present study, we set up a 40% MVC as the target level to reduce the further any potential bias. If MVC target level were so high, the endurance time would be shortened, and the change of the mean frequency decreased, so that the result would not be statistically significant.35
In contrast, if MVC target level was so low, the endurance time would be lengthened, then the attention of the subject to the test is decreased, and the occurrence of error might be a possibility.
Our results confirmed significant differences in muscle fatigability between the DD and II groups, but not between II and ID or between ID and DD. However, we showed positive trends to get greater frequency change and to get shorter endurance time, in the order of II, ID and DD genotypes.
Because the DD type has a relatively higher proportion of fast-twitch fibers than II type, The DD type with the biggest mean frequency change might have less resistance to muscle fatigue than II type. In other words, it means that the DD type has lower muscle endurance than that of II. On the contrary, the II genotype is also associated with more slow-twitch fibers, which are more efficient. This may be a mechanism for the tendency to get longer endurance time of muscular contraction in II genotype.
Nevertheless, it has been suggested that the ACE genotype is related to both muscle endurance and strength, in the previous studies. Why is the ACE genotype associated with not the muscle strength, but only the muscle endurance in our study? The reasons are far from clear-cut, but we presume that the muscle endurance, rather than muscle strength, was more affected by genetic factors, especially in the elderly, because older people have relatively higher proportion of slow-twitch fibers compared to younger people, regardless of ACE genotypes, as increasing age is accompanied by a greater loss of contractile material of fast-twitch type than that of slow-twitch type fibers.11
To our knowledge, there has been no other study, except this study, which aimed at the evaluation of the association among the ACE polymorphism, ACE activity and muscular endurance by an objective quantification of the muscle fatigability.
Also, this study has significance in terms of trying to postulate the effect of the ACE genotypes on muscle strength through the grip strength and body composition, alongside the muscle fatigability. Further, the correlation between the ACE genotypes and physical performance level was examined. In this way, it was considered that our study is significant as a multiple-dimensional model.
However, there are several limitations in the interpretation of the result in this study. First, the subjects who participated in the research were relatively small in numbers. Therefore, these results cannot be reflect the characteristics of the general population. In addition, due to the limitations of a sample size, the nonparametric statistics were used. Even though this study shows similar results from that of the earlier studies, there were some limitations on its statistical significance.
Secondly, the ACE activity measured by this study was ACE levels of the circulating blood. Therefore, it can differ from that of the ACE activity inside the real skeletal muscle. Angiotensin II, affecting at the skeletal muscle through venous by locally produced blood, had a greater influence than the systemic circulation. Therefore, because of the ACE level on the local skeletal muscle had more significant effect on the muscle endurance and strength,36
we need to further investigate the evaluation of the ACE activity on skeletal muscle by muscle biopsy.
Thirdly, the serum calcium, phosphorus, and magnesium, which have an effect on the muscular endurance, was not considered in the present study.
Finally, because this study is targeted at the 65-years-old people, it can become an advantage of this research, owing to exclude the effect of age on muscle function. But at the same time, it is the limit that there is no comparison with the other age groups.