PONE-D-24-24207Association between Angiotensin-(ACE) insertion/deletion polymorphism and hypertension in a Ghanaian populationPLOS ONE

Dear Dr. Bonney,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

Please submit your revised manuscript by Sep 15 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Sepiso Kenias Masenga, PhD

Academic Editor

PLOS ONE

Journal requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. We note that your Data Availability Statement is currently as follows: [All relevant data are within the manuscript and its Supporting Information files.]

Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).

For example, authors should submit the following data:

- The values behind the means, standard deviations and other measures reported;

- The values used to build graphs;

- The points extracted from images for analysis.

Authors do not need to submit their entire data set if only a portion of the data was used in the reported study.

If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories.

If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access.

3. PLOS ONE now requires that authors provide the original uncropped and unadjusted images underlying all blot or gel results reported in a submission’s figures or Supporting Information files. This policy and the journal’s other requirements for blot/gel reporting and figure preparation are described in detail at https://journals.plos.org/plosone/s/figures#loc-blot-and-gel-reporting-requirements and https://journals.plos.org/plosone/s/figures#loc-preparing-figures-from-image-files. When you submit your revised manuscript, please ensure that your figures adhere fully to these guidelines and provide the original underlying images for all blot or gel data reported in your submission. See the following link for instructions on providing the original image data: https://journals.plos.org/plosone/s/figures#loc-original-images-for-blots-and-gels.   

In your cover letter, please note whether your blot/gel image data are in Supporting Information or posted at a public data repository, provide the repository URL if relevant, and provide specific details as to which raw blot/gel images, if any, are not available. Email us at plosone@plos.org if you have any questions.

4. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. 

5. We notice that your supplementary figures are uploaded with the file type 'Figure'. Please amend the file type to 'Supporting Information'. Please ensure that each Supporting Information file has a legend listed in the manuscript after the references list.

6. Please upload a copy of Fig 1-Gel and Fig 1- ACE , to which you refer in your text on page 7 and 12. If the figure is no longer to be included as part of the submission please remove all reference to it within the text.

7. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

1. Please follow the STROBE checklist and add it as supplementary file

2. We note that your Data Availability Statement is currently as follows: All relevant data are within the manuscript and its supporting information files.

Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).

3. When completing the data availability statement of the submission form, you indicated that Yes - all data are fully available without restriction. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If you are unable to adhere to our open data policy, please kindly revise your statement to explain your reasoning and we will seek the editor's input on an exemption. Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Article Title

Association between Angiotensin-(ACE) insertion/deletion polymorphism and hypertension in a Ghanaian population

Study Summary

This case-control study conducted by Bonney et al. at Tamale Central Hospital investigates the relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and essential hypertension in the Ghanaian population. The study sample size was 144 participants, comprising 72 hypertensive patients and 72 normotensive individuals. The finding of the study was that the DD genotype was significantly associated with an increased risk of hypertension. The finding suggests the potential of ACE I/D polymorphism as a biomarker for hypertension.

Major Strengths of the study

The study effectively addresses a significant gap in the literature by focusing on the Ghanaian population, which is underrepresented in genetic studies on hypertension. The case-control design and the utilization of logistic regression to adjust for confounders enhance the validity of the study findings.

Minor Comments

1. The authors should consider adding a section on the limitations of the study, including potential biases, to increase transparency and help readers critically evaluate the findings within the appropriate context.

Reviewer #2: Manuscript/paper title: Association between Angiotensin-(ACE) insertion/deletion polymorphism and hypertension in a Ghanaian population.

Summary statement of the article:

The article explores the relationship between ACE I/D polymorphism and essential hypertension among patients in Ghana. This case-control study involved 144 participants, including 72 hypertensive patients and 72 normotensive individuals. The findings revealed that the DD genotype significantly increased the risk of hypertension, with an adjusted odds ratio of 8.52. The study concluded that the presence of the DD genotype is strongly associated with an increased risk of hypertension in the Ghanaian population. The research highlights the importance of genetic factors in the pathophysiology of hypertension and suggests that ACE I/D polymorphism could serve as a biomarker for early diagnosis and prevention of hypertension complications.

Specific areas of improvement

Major comments:

1. I encourage the authors to rewrite the abstract, i must say it is well written and concise but adding some more flesh would make the article more credible.

2.Citations: Authors should ensure that all statements are cited, as this rules out the practice of plagiarism in the article. Starting with the first statement under the “Introduction section.”

3. Statistical Analysis: Authors should provide more detailed explanations of the statistical methods used, including any software or tools employed for the analysis. They have mentioned some statistical tests that were employed but not the specific tools/software, e.g. SPSS/STATA version 1. Etc...

4. Under the data analysis section, authors have emphasized that they considered data to be statistically significant at P-value < 0.05. However, this has not been shown in Table “6: Logistic regression analysis of the ACE polymorphism.” Please show the P-Values in Table 6, for clarity and proof that indeed the results truly represent what has been researched.

5. Figures and Tables: Ensure that all figures and tables are clearly labelled and referenced in the text. Consider uploading clearer figures to enhance the presentation of data.

• “Table 1: Primer sequence used in PCR amplification of ACE I/D polymorphism.” If authors could try to make clearer narrations, it would be hard to understand.

• Figure 1, insert it closer to where the description is. Do this for all tables and figures.

• Authors should consider the input of narrations to all tables attached to this article that are articulate and easy to follow.

• All the figures that have been uploaded are not clear including their narrations. It makes readers think that they were downloaded from the internet and pasted. Authors, please work on that too.

6. Under 2.3 Data collection procedure, the authors must ensure to include the (WHO Step questionnaire for chronic diseases) and the WHO staging tool that has been referred to have been used. I advise that these be included as part of the supplementary files or provide a link or cite, as this will help in the clarity of the article to the readers.

7. Under 2.3 Data collection procedure, the statement - “BMI was classified into five categories according to the WHO (2008) guidelines: underweight (<18.5 kg/m-2), normal (18.5-24.9 kg/m-2), overweight (25.0 - 29.9 kg/m-2) and obese (≥30.0 kg/m-2).” The authors have mentioned that they used 5 categories of classification, but only 4 have been mentioned, please clarify this.

8. Discussion Depth: Expand the discussion to include more comparisons with similar studies in other populations, highlighting the significance of the findings in the context of existing literature.

Minor Corrections:

1. Authors should ensure any terminologies are defined at first use. E.g. K3EDTA has not been defined. Please look into all terms that might have been left out.

2. Check for any grammatical errors or awkward phrasing in the summary. Clarity and readability are essential.

3. What were the limitations and strengths of this research? Adding these sections will improve the clarity of the article including its reproducibility.

4. Consider page alignment and justification in the article, especially for the results tables. Authors can consider other tables being in a landscape mode.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Lweendo Muchaili

Reviewer #2: Yes: Bislom Chikwanka Mweene

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Association between Angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and hypertension in a Ghanaian population

PONE-D-24-24207R1

Dear Dr. Bonney,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Sepiso K. Masenga, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: