Reviewer's report
Title: The influence of ACE ID and ACTN3 R577X polymorphisms on
lower-extremity function in older women in response to high-speed power
training
Version: 2
Date: 11 June 2013
Reviewer: Matthew J Delmonico
Reviewer's report:
Major Compulsory Revisions
1. While this study by itself seems to be well-conducted, with a valid rationale, I
was wondering why these two phenotypes (S10 and GUG) were not included in
your group’s prior publication that you referenced “[21]” in AGE journal (July
2012)? In that publication, it appears that you did the exact same type of
analysis (i.e. effect of ACE and ACTN3 polymorphisms on muscle power
phenotypes and a physical function phenotype – 30 s sit to stand test) with the
same study. It seems clear that data on these phenotypes were collected during
the course of that study given that it was an intervention study and these
phenotypes would have fit well into that paper. I think that the similarities
between the two papers (i.e. muscle and physical function phenotypes), while
not identical in the phenotype data reported, might not be distinct enough for
this new one to meet the minimum publishable unit threshold. Can you justify
why this paper should stand alone and why these measures were not included
in your previous publication?
Thanks for your comments that greatly helped us to improve the overall quality
of this article. These two phenotypes (S10 and GUG) were not included in our
prior publication in AGE journal (July 2012) due to the extension of the training
program and extensive discussion. Also because in the first one we tried to
focus on muscular performance. Besides, after having performed all measures,
observing what happened in the other variables,, it was intended to show that
according to some critical points of view regarding the genetic association
studies, this second article is purposely directly to discussion/ implications of
capacity function in lower limbs, as a pertinent thematic that surely deserves
this prominence. Furthermore, we focus the present article on the variables that
best show the nature of gait speed and a mobility measure in older people and
analyze their effect in ACE and ACTN3 polymorphism. According to the present
revisions, we will try to clarify this sentence, as the Reviewer stated, readers
would necessarily equate power phenotypes with walking velocity.
2. The last sentence of the Results section of the Abstract does not make sense
to me.
The Reviewer is absolutely right. As recommended, we rewrite the paragraph
that may confuse readers.
3. Abstract Conclusion: It does not appear that your paper’s data support that
these phenotypes are related to “exercise-related power phenotypes” as they
are not part of this paper. Did you mean walking velocity? I don't think that most
readers would necessarily equate power phenotypes with walking velocity.
The Reviewer is absolutely right. As recommended, we rewrite the conclusion in
abstract and removed the classification of power to gait speed phenotype and
mobility trait.
4. Background. The second to last paragraph states that an aim is (using a
genotype effect/ interaction) to predict disability or muscle weakness. This does
not appear to be what your paper was about given that you did not have a
clinically defined disability outcome (gait speed could be but your cohort is high
functioning) or a muscle strength phenotype. You assessed gait speed and a
mobility measure. I think that you stated your aim better in the first paragraph of
the methods section.
The Reviewer is absolutely right. As recommended, we rewrite the aim
described in Background. We removed the term effect/ interaction to predict
disability or muscle weakness taking to account the first paragraph of the
methods section.
5. Background. I found the last paragraph to be confusing. The first sentence
sounds like a specific aim, not a hypothesis. Thus, I only see one hypothesis.
The last paragraph, second sentence should read “One of the hypotheses is...”
– this assumes that you have more than one. Regarding this hypothesis, with
complex phenotypes such as gait speed and GUG, how can you be certain that
these are exclusively due to “a higher muscle phenotype effect” (I am not sure
what you mean by that phrase) or some other factor (e.g. nervous system,
comorbidities, medications, etc)? Finally, the last sentence should also read
“...explain the interindividual...”
The Reviewer is absolutely right. As recommended, we rewrite the last
sentence explaining better our purpose in accordance to the revisions.
6. Methods – lower extremity function. The first sentence does not make sense
to me.
The Reviewer is absolutely right. As recommended, we rewrite the first
description of the test.
7. Discussion: The first paragraph of the discussion needs to be re-worked to
highlight the unique findings of the current investigation rather than the
introduction-like feel that it currently has. Secondary findings should be in the
second paragraph and please avoid re-stating results as done in the third
paragraph. Additionally, a paragraph needs to be more than one sentence, so
put paragraphs 6 and 7 somewhere else.
The Reviewer is absolutely right. We rewrite the first paragraph of the
discussion in order to highlight the unique finding of the current investigation.
It was also add a second paragraph with secondary findings. We also avoid the
results, and reduced all paragraph.
We also change paragraphs 6 and 7 to paragraphs before.
8. Discussion: In your limitations section, you mentioned the need to include
other muscle function measures. However, you previous paper had them.
The Reviewer is absolutely right. As recommended, we rewrite the second
limitation “Secondly, according to muscle function, these measures should be
analyzed in older people with functional limitations to compare and observe if
the training has the same effect in the present genotypes."
9. Discussion: In your last sentence of this section, you state that this “...study
confirms the importance of identifying individuals vulnerable to the effects of
aging and thus exposed to a greater decline in muscle function.” You study was
not an “aging” study as it did not study the effects of aging, only the effect of a
12 wk intervention.
The Reviewer is absolutely right. As recommended, we removed term aging
and rewrite the final sentence: “…the effects of a 12 week intervention in gait
speed and mobility in older people.”
Minor Essential Revisions
1. Abstract and Methods: “One hundred and thirty-nine” should be replaced with
“One hundred thirty-nine”
The Reviewer is absolutely right. As recommended we corrected the number.
2. Background: The third sentence states that “Recently, two systematic
reviews [1, 5]...” Ref 1 is a 2001 article. Should this be considered “recent”?
The Reviewer is absolutely right. We removed the term recently.
3. Discussion. Paragraph 8 is long and should be broken up into two
paragraphs.
The Reviewer is absolutely right. As recommended we had broken the
paragraph into two paragraphs.
Discretionary Revisions - none
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests: I declare that I have no competing
interests
Reviewer's report #2
Title: The influence of ACE ID and ACTN3 R577X polymorphisms on
lower-extremity function in older women in response to high-speed power
training
Version: 2
Date: 16 June 2013
Reviewer: Joseph Devaney
Reviewer's report:
Major Compulsory Revisions
Is there a description of the results of the study without accounting for ACTN3
genotype? This publication should be cited. Were there any non-responders?
First, thanks for your comments that greatly helped us to improve the overall
quality of this article.
We don’t have results of the present study without accounting for ACTN3.
Because the purpose was to analyze both genotypes (single and combined).
P-values need numerical value for the training effects.
The Reviewer is absolutely right. We add numerical values (P=0.001).
The discussion needs to add more biology behind the results. The discussion
reads more like a results section.
The Reviewer is absolutely right. We add and rewrite some biology facts behind
the results. And rewrite the exposition of the results.
For example, the sentence "Compared to the ACTN3 R577X polymorphism, a
significant interaction for genotype training was also evident only in S10 and not
in the GUG test (P=0.044 and P=0.477, respectively)" is in the discussion but is
not expanded to include any biological reason for the results.
The Reviewer is absolutely right. According to the revision in this topic, the
discussion was improved.
Statements like "On performing this experiment, older women tend to focus on
maintaining balance in rising from the chair and may disregard high velocity
execution. Also might be that the posture control (i.e. sensorial system) play a
major role in it." Is there any data that has been collected or publications that
can be used to verify these statements?
The Reviewer is absolutely right. According to Davids, K., P. Glazier, et al.
(2003). "Movement systems as dynamical systems: the functional role of
variability and its implications for sports medicine." Sports Med 33(4): 245-260,
it is pertinent this analysis and also as we affirm, balance and coordination
might are specific capacities that can predict some difference between the
subjects. Coordination reporting is an alternative approach for interpreting the
inter-individual in motor behaviour during each unique performance. Genetic
studies and training seems to be the best way to show where this variation is
highlighted. Their interaction is still to be verified but we think that new studies
and in the future research area may supporting physical performance and other
complex phenotypes.
The statement "It seems that #-actinin-3 expression may affect muscular
capacity, which implies that #-actinin-2 may compensate for this deficiency and
neutralize the phenotypic consequences at baseline". What does the term
baseline signify?
Baseline is an initial value of the measurements, that can be used to compare
past, current and projected future values and it’s used as a basis for
comparison. It’s a reference point against which other measures can be
evaluated.
The baseline can be considered the starting point against which all future
values are measured.
This statement needs to be removed "Our study was also able to show how the
ACTN3 protein makes functional contributions to muscular power...". The paper
does not show any protein work or cite any protein work.
The Reviewer is absolutely right. As recommended we removed the statement.
Minor Essential Revisions
The should be more specifics about the Inclusion criteria. The term "older"
needs to be defined. What if there were marathon runners? This is a type of
exercise training and may have an effect on response to RT.
The Reviewer is absolutely right. Based on age range we used “older” instead
of elderly because the average age of our participants was 64 (in the end of the
spectrum). We adjusted the terms accordingly to this age range: middle aged is
consider 30-40 years, old 55-65 years and elderly 75 and up. However, the
problem is that chronological age does not correlate perfectly with functional
age, i.e. two people may be of the same age, but differ in their mental and
physical capacities. According to scientific research in sport science and
gerontology, we followed the purpose of Häkkinen et al. (1998), once they used
in their study, women (W) divided into two age groups, i.e., middle age: W40
(39±3) and older: W70 (67±3). Häkkinen et al. (1997) used 10 older (O) men
(61 +/- 4 yrs) and denominated 12 elderly women (68 +/- 4 yrs; W70). Besides,
Henwood et al. (2008) used 38 healthy independent older adults (65-84 years)
so, as the subjects of our study are not oldest ut the mean ± SD ages are 64
plus 65 years, we believe that our results may be applied to the elderly
population in general. We tried to be consistent and use older term.
The description of the allele frequencies needs to include a reference to
hapmap or 1000 genome project.
As recommended we added the reference according to: “Wood, A. R., J. R.
Perry, et al. (2013). "Imputation of Variants from the 1000 Genomes Project
Modestly Improves Known Associations and Can Identify Low-frequency
Variant - Phenotype Associations Undetected by HapMap Based Imputation."
PLoS One 8(5): e64343.” We also corrected all references in general.
The sentence in the discussion that starts.."For that reason, it would be relevant
in the older women, identifying genotypes associated with functional capacity
declines..." needs to be rewritten.
The Reviewer is absolutely right. As recommended we rewrite the sentence in
the discussion.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests: I declare that I have no competing
interests