PONE-D-20-12583

Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging

PLOS ONE

Dear Dr. Itoh,

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Hiroyuki Itabe, Ph.D.

Academic Editor

PLOS ONE

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"This work was supported by "Center for Innovation Program" of the Japan Science and Technology Agency Grant Number JPMJCE1302 (to SN and KI).

SN: Shigeyuki Nakaji, KI: Ken Itoh.

URL (https://www.jst.go.jp/EN/index.html)

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

   

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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: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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

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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: Authors conducted well designed study with enough subject number. Results from their study enhanced new insight into roll of Nrf2 in atherosclerosis. This reaches standards of published in peer-reviewed journal. Thank you.

Reviewer #2: The authors examined baPWV, an indicator of vascular stiffness and SNPs in the NRF gene SNP-617 and showed the clear association of NRF activity and arterial stiffness. However, some issues written below are still concerned.

Major:

1. The authors showed the clear relationship between baPWA and SNP-617 in people under 60 years old. However, if it is true, this relationship should become clearer in people over 60 years old, which may become more important in terms of prevention of cardiovascular disease.

2. Although the authors described in the limitation of the study, it is not clear whether there is a gender difference in the results of baPWV, SBP, MAP and PP.

3. It is relatively easy to understand there is a relationship between SNP-617 and arterial stiffness, but hard to connect it to creatinine and HDL cholesterol levels.

Minor:

1. P6, l11 oxidative stress: under the condition of oxidative stress?

2. P10, l5 SBP pressure: delete pressure

3. P13, l14 CA, 1317/1169-1589: change to AA,

4. P14, l16 *p<0.01: change to **p<0.01

5. P22, l16 creatinine HDL cholesterol: insert and between creatinine and HDL cholesterol

6. P22, l18 AA, CA, and CC: change to AA, CA and CC

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Reviewer #1: No

Reviewer #2: No

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Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging

PONE-D-20-12583R1

Dear Dr. Itoh,

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.

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Kind regards,

Hiroyuki Itabe, Ph.D.

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. 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 #2: Yes

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

Reviewer #2: Yes

**********

4. 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 #2: Yes

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5. 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 #2: Yes

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6. 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 #2: The authors have appropriately addressed all comments the reviewers made and have revised the manuscript well.

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7. 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 #2: No