Review for 10.1186/s12876-018-0922-8 (2019)

Reviewer ’s report  
 
Title:  The impact of the rs8005161 polymorphism on G protein -coupled receptor GPR65 
(TDAG8) pH -associated activation in i ntestinal inflammation  
 
Version: 0 Date: 11 Apr 2018 
 
Reviewer:  Maikel  Peppelenbosch  
 
Reviewer’s report:  
 
This is an interesting manuscript linking genotype to signal tran sduction phenotype, well written 
and I enjoyed reading it.  
 
- The Rho activation experiments would benefit from a positive control, e.g. LPA, as to get a 
feeling as to how physiological relevant the measured signals are  
 
_ Maybe a missed chance in the mech anistic discussion is that GPR65 -mediated G12/13 
signalling probably also provokes Rac inhibition (e.g. Sugimoto N, Takuwa N, Okamoto H, 
Sakurada S, Takuwa Y. Mol Cell Biol. 2003 Mar;23(5):1534 -45) while Rac inhibition per se 
seems beneficial in IBD (Parik h  et aL. Suppression of p21Rac signaling and increased innate 
immunity mediate remission in Crohn's disease. Sci Transl Med. 2014 Apr 23;6(233):233ra53.), 
probably this is relevant to the current srudy  
 
- cAMP production can be quite sensitive to NSAID us e. Is there information on the use of 
aspirin etc. in the volunteers for the study?  
 
Are the methods 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 statistical review is recommended, please specify what aspects require further 
assessment in your commen ts 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 
manus cript, 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 of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any p atents 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 i nterests?  
 
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 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 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 as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal