Reviewer ’s report  
 
Title:  Genetic variation and expression levels of tight junction genes identifies association 
between MAGI3 and inflammatory bowel disease  
 
Version: 0 Date: 20 Oct 2016 
 
Reviewer:  Radhakrishna  Rao 
 
Reviewer’s report:  
 
Authors in this study have investigated the single nucleotide polymorphism located in genes 
encoding interacting TJ proteins and corresponding expressions in relation to inflammatory 
bowel disease.  Gene expression analyses were performed to correlate with in flammatory status 
and medical treatment.  SNPs in MAGI2 and MAGI3 genes were in highest relation with IBD, 
especially inflammatory status; decreased expression levels of MAGI3 along with PTEN and 
TJP1 with inflammation and the opposite with PTPN22 expressi on.  The study is well executed, 
population size is very good, and the results are interesting.  I believe the outcome of the study 
does contribute the advance of the field.  However, following issues needs to be addressed.  
 
1. MAGI2, MAGI3 and TJP1 are al l tight junction associated proteins.  PTEN and PI3K are 
known to play crucial role in regulation of tight junction integrity.  So, the major genes affected 
are directly related to tight junction integrity and paracellular permeability, which is known to b e 
a crucial factor in the pathogenesis of IBD.  This aspect of discussion needs to be elaborated in 
the Discussion section.  
 
2. Tables are little hard to understand without reading the text in the results.  Although these 
tables will be inserted close to th e text, it would be reader friendly if the columns and rows better 
described at the bottom of the table itself.  This I think will also attract non -clinical and non -
genetic readers.  
 
Are the m ethods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary 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.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional sta tistical 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:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past 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 that may in any way gain or lose 
financially from the publication o f 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, fees, 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 paper?  
 
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 the journal. I understand that my name wil l 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 und er an 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 a s 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:  Genetic variation and expression levels of tight junction genes identifies association 
between MAGI3 and inflammatory bowel disease  
 
Version: 0 Date: 20 Oct 2016 
 
Reviewer:  Radhakrishna  Rao 
 
Reviewer’s report:  
 
Authors in this study have investigated the single nucleotide polymorphism located in genes 
encoding interacting TJ proteins and corresponding expressions in relation to inflammatory 
bowel disease.  Gene expression analyses were performed to correlate with in flammatory status 
and medical treatment.  SNPs in MAGI2 and MAGI3 genes were in highest relation with IBD, 
especially inflammatory status; decreased expression levels of MAGI3 along with PTEN and 
TJP1 with inflammation and the opposite with PTPN22 expressi on.  The study is well executed, 
population size is very good, and the results are interesting.  I believe the outcome of the study 
does contribute the advance of the field.  However, following issues needs to be addressed.  
 
1. MAGI2, MAGI3 and TJP1 are al l tight junction associated proteins.  PTEN and PI3K are 
known to play crucial role in regulation of tight junction integrity.  So, the major genes affected 
are directly related to tight junction integrity and paracellular permeability, which is known to b e 
a crucial factor in the pathogenesis of IBD.  This aspect of discussion needs to be elaborated in 
the Discussion section.  
 
2. Tables are little hard to understand without reading the text in the results.  Although these 
tables will be inserted close to th e text, it would be reader friendly if the columns and rows better 
described at the bottom of the table itself.  This I think will also attract non -clinical and non -
genetic readers.  
 
Are the m ethods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary 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.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional sta tistical 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:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past 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 that may in any way gain or lose 
financially from the publication o f 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, fees, 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 paper?  
 
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 the journal. I understand that my name wil l 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 und er an 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 a s 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:  Genetic variation and expression levels of tight junction genes identifies association 
between MAGI3 and inflammatory bowel disease  
 
Version: 0 Date: 20 Oct 2016 
 
Reviewer:  Radhakrishna  Rao 
 
Reviewer’s report:  
 
Authors in this study have investigated the single nucleotide polymorphism located in genes 
encoding interacting TJ proteins and corresponding expressions in relation to inflammatory 
bowel disease.  Gene expression analyses were performed to correlate with in flammatory status 
and medical treatment.  SNPs in MAGI2 and MAGI3 genes were in highest relation with IBD, 
especially inflammatory status; decreased expression levels of MAGI3 along with PTEN and 
TJP1 with inflammation and the opposite with PTPN22 expressi on.  The study is well executed, 
population size is very good, and the results are interesting.  I believe the outcome of the study 
does contribute the advance of the field.  However, following issues needs to be addressed.  
 
1. MAGI2, MAGI3 and TJP1 are al l tight junction associated proteins.  PTEN and PI3K are 
known to play crucial role in regulation of tight junction integrity.  So, the major genes affected 
are directly related to tight junction integrity and paracellular permeability, which is known to b e 
a crucial factor in the pathogenesis of IBD.  This aspect of discussion needs to be elaborated in 
the Discussion section.  
 
2. Tables are little hard to understand without reading the text in the results.  Although these 
tables will be inserted close to th e text, it would be reader friendly if the columns and rows better 
described at the bottom of the table itself.  This I think will also attract non -clinical and non -
genetic readers.  
 
Are the m ethods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary 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.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional sta tistical 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:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past 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 that may in any way gain or lose 
financially from the publication o f 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, fees, 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 paper?  
 
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 the journal. I understand that my name wil l 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 und er an 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 a s confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
assistant