Reviewer ’s report 
 
Title: CTRC gene polymorphism (p.G60=; c.180 C>T) in acute pancreatitis  
 
Version: 1 Date: 07 Jul 2016  
 
Reviewer: Atsushi Masamune  
 
Reviewer's report:  
 
This study might be potentially interesting, but it is disappointing that the authors did not present 
convincing data that this CTRC variant is a dangerous one in AP.  
 
 
1. One of the novelty of this study is that there were no patients with moderate or sev ere AP 
in subjects carrying the TT genotype. However, the number of these subjects was only 5. 
The distribution of the variants and the severity was not significantly associated, 
indicating that the conclusion of the authors is misleading. It is reasonable  to assume that 
a synonymous CTRC variant will not affect the progression from mild to severe course of 
the disease, because it has no relation to proinflammatory mediators.  
 
 
2. It is unclearly how the presence of chronic pancreatitis was excluded. Consider ing that 
the authors have published similar article dealing with CP, this point should be carefully 
excluded.  
 
 
3. Clinical courses of AP were not presented in detail at all.  
 
 
4. The details of detected mutations in the SPINK1, CFTR and missing.  
 
 
5. Overall, t he manuscript is redundant. For example, in Introduction, name of pancreatitis -
associated mutations are repeatedly described.  
 
 
6. Statistics: The authors should have used Fisher's 2X3 model, but not 2X2 model for the 
comparison of this variant between the c ontrols and total patients with CP.  
 
 
7. The polymorphism should be shown as "c.180C>T", but not "c.180" throughout the 
manuscript.  
 
8. Recurrence of AP depends on the remaining biliary stones in the cases of biliary AP. Did 
the patients with biliary AP under go cholecystectomy or endoscopic treatment ?  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the neces sary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to asse ss any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the pa st five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, f ees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this p aper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of t he journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under a n Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report 
 
Title: CTRC gene polymorphism (p.G60=; c.180 C>T) in acute pancreatitis  
 
Version: 1 Date: 07 Jul 2016  
 
Reviewer: Atsushi Masamune  
 
Reviewer's report:  
 
This study might be potentially interesting, but it is disappointing that the authors did not present 
convincing data that this CTRC variant is a dangerous one in AP.  
 
 
1. One of the novelty of this study is that there were no patients with moderate or sev ere AP 
in subjects carrying the TT genotype. However, the number of these subjects was only 5. 
The distribution of the variants and the severity was not significantly associated, 
indicating that the conclusion of the authors is misleading. It is reasonable  to assume that 
a synonymous CTRC variant will not affect the progression from mild to severe course of 
the disease, because it has no relation to proinflammatory mediators.  
 
 
2. It is unclearly how the presence of chronic pancreatitis was excluded. Consider ing that 
the authors have published similar article dealing with CP, this point should be carefully 
excluded.  
 
 
3. Clinical courses of AP were not presented in detail at all.  
 
 
4. The details of detected mutations in the SPINK1, CFTR and missing.  
 
 
5. Overall, t he manuscript is redundant. For example, in Introduction, name of pancreatitis -
associated mutations are repeatedly described.  
 
 
6. Statistics: The authors should have used Fisher's 2X3 model, but not 2X2 model for the 
comparison of this variant between the c ontrols and total patients with CP.  
 
 
7. The polymorphism should be shown as "c.180C>T", but not "c.180" throughout the 
manuscript.  
 
8. Recurrence of AP depends on the remaining biliary stones in the cases of biliary AP. Did 
the patients with biliary AP under go cholecystectomy or endoscopic treatment ?  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the neces sary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to asse ss any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the pa st five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, f ees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this p aper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of t he journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under a n Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report 
 
Title: CTRC gene polymorphism (p.G60=; c.180 C>T) in acute pancreatitis  
 
Version: 1 Date: 07 Jul 2016  
 
Reviewer: Atsushi Masamune  
 
Reviewer's report:  
 
This study might be potentially interesting, but it is disappointing that the authors did not present 
convincing data that this CTRC variant is a dangerous one in AP.  
 
 
1. One of the novelty of this study is that there were no patients with moderate or sev ere AP 
in subjects carrying the TT genotype. However, the number of these subjects was only 5. 
The distribution of the variants and the severity was not significantly associated, 
indicating that the conclusion of the authors is misleading. It is reasonable  to assume that 
a synonymous CTRC variant will not affect the progression from mild to severe course of 
the disease, because it has no relation to proinflammatory mediators.  
 
 
2. It is unclearly how the presence of chronic pancreatitis was excluded. Consider ing that 
the authors have published similar article dealing with CP, this point should be carefully 
excluded.  
 
 
3. Clinical courses of AP were not presented in detail at all.  
 
 
4. The details of detected mutations in the SPINK1, CFTR and missing.  
 
 
5. Overall, t he manuscript is redundant. For example, in Introduction, name of pancreatitis -
associated mutations are repeatedly described.  
 
 
6. Statistics: The authors should have used Fisher's 2X3 model, but not 2X2 model for the 
comparison of this variant between the c ontrols and total patients with CP.  
 
 
7. The polymorphism should be shown as "c.180C>T", but not "c.180" throughout the 
manuscript.  
 
8. Recurrence of AP depends on the remaining biliary stones in the cases of biliary AP. Did 
the patients with biliary AP under go cholecystectomy or endoscopic treatment ?  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the neces sary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to asse ss any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the pa st five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, f ees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this p aper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of t he journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under a n Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant