Reviewer's report
Title:Synaptosomal-Associated Protein 25 (Snap-25) Gene Polymorphism
prevalence in fibromyalgia syndrome and relationship with clinical symptoms
Version:2Date:14 February 2014
Reviewer:Montserrat Mila
Reviewer's report:
Synaptosomal_Associated Protein 25 (Snap-25) Gene Polymorphism prevalence
in fibromyalgia syndrome and relationship with clinical symptoms
Major Comments:
1.This manuscript is very difficult to understand. It is not well written, nor is it well
structured.
Manuscript was evaluated as the reviewer asked. Necessary changes were done.
2. The title should be changed; prevalence should be changed to frequency.
Title was changed as the reviewer indicated. Title was changed into ‘SynaptosomalAssociated Protein 25 (Snap-25) Gene Polymorphism frequency in fibromyalgia
syndrome and relationship with clinical symptoms’
3. There is neither an objective nor a hypothesis.
Objective of our study was added to the manuscript as the reviewer asked.
‘’ Objectives: We aimed to study SNAP-25 gene polymorphism, which is related to
many psychiatric diseases, and FMS association in this prospective study.
(moreover, we extended our objective in the 5th article)
4. MnI T/G should be changed to the corresponding rs.
MnlI (rs3746544) and DdeI (rs1051312) were stated in background and molecular
analysis parts of the manuscript.
5. The conclusion “FMS etiopathogenesis is not clearly known. Numerous
neurologic, cognitive and psychological disorders were found during cause
intended studies. Our study showed increased SNAP-25 Ddel T/C genotype
which is related with personality disorders, behavioral symptoms and
psychological disorders that can develop later in life in FMS patients when
compared with the control group” is not deduced from the present work.
Moreover, all patients and controls are around 40 years old. This is not “later in life” .
Translation of the manuscript was deficient. It was lost in translation. There is not a
phrase in English that can be used instead. For this reason, “in life” part was
removed from the manuscript, we are sorry for the inconvenience.
It is difficult to understand how the authors relate the presence of fibromyalgia, the
results of the psychological test and the molecular studies.
Psychiatric symptoms are very common in fibromyalgia syndrome. In addition, FMS
and psychiatric symptoms association is a valuable discussion field still. There are
different views on this matter. One of them is the mutual pathophysiology in FMS and
psychiatric disorders. Several neurotransmitter system pathological changes were
showed for this mutual physiopathogenetic factor. Dopamin and serotonin mediated
pain conduction and gene polymorphisms that affect these neurotransmitters levels
can be among these biological factors. SNAP25 protein is critical in plasma
membrane and synaptic vesicle fusion. Several studies investigated the relationship
between SNAP25 gene polymorphism and personality disorders, schizophrenia and
attention deficit and hyperactivity development. Moreover, SNAP25 protein is related
to other neurotransmitter functions (eg. dopamin and serotonin) due to its
involvement in vesicle membrane transport and fusion. Dopamin is an important
mediator for both psychopathologic cases and pain conduction. For this reason
SNAP-25 gene polymorphism can be the responsible for psychiatric disorders and
FMS pathogenesis. we built the study on this thought.
6. I'm not a statistician and therefore this part should be evaluated by an expert in
this field. However I think a multivariate test should be applied to relate all the
parameters.
Manuscript was evaluated by a statistician. In this study:
We found DdeI (rs 1051312) gene TC genotype prevalence higher in the patient
group. For this reason we compared SF-36, VAS, BDS scores in patients h-who has
TC genotype and who has not. Sub parameters of SF-36 did not show significant
difference; however, VAS and BDS scores were higher in TC genotype group.
Genotype can influence VAS and BDS, but VAS and BDS can not affect genotype.
We did not perform linear regression because it is contrary to reason and result
nature. The table is shown below, if you would like to examine:
Wald
VAS
0.665
BDS
1.067
Success rate=%66,7
Cox&Snell R2=0,049
p
Odds ratio
0.415
0.302
0.981
0.972
%95 CI
sub limit
0.0938
0.920
%95 CI
Super limit
1.027
1.026
Minor points:
1.It is not necessary to describe all the results in the abstract, only the most
relevant.
Abstract results were shortened as the reviewer asked.
2.The references are not updated. There is one reference from 1984.
References were revised, and recent references were given.
3.Table 1 is not referenced in the text.
Table 1 is referenced in the text.
4.The results would be clearer if shown in tables.
Results were given as tables.
5.The tables should be carefully revised, there are some % missing.
Tables were revised.