Dear Dr Enzo Montanero,

Thank you for considering the revised version of our manuscript ACE variants and risk of Cardiovascular Disease, by Sarah H. et al. for publication in Atherosclerosis. We are thankful to the referees and the Editor for pointing out some important modifications needed in the report. We have thoughtfully taken into account these comments. The explanation of what we have changed in response to the reviewers’ concerns is given point by point in the following pages.

We believe that the comments have been highly constructive and very useful to restructure the manuscript. We also believe that the new data included in the article really improved the quality of both our genetic and functional analysis. Indeed, we now show that the A allele of the rs10947 SNP of the ACE gene is a risk factor for all etiologies of cardiovascular disease (the association in the overall population resisted correction for multiple testing by Bonferroni). Moreover, we now show that mRNA levels of the ACE gene are higher in MI cases during the acute phase than in healthy controls or MI cases 3 months after the event. and IS cases in the stable condition.

We hope that all these changes fulfil the requirements to make the manuscript acceptable for publication in Atherosclerosis.

Looking forward to hearing from you soon.

Sincerely yours,

Sarah H. and Lucas Delphino on behalf of the authors.

Corresponding author: Lucas Delphino at Alzheimer’s Disease Laboratory, Marie Curie Research Institute, 75000, Paris, France, xxx@mariecurie.fr, phone number: +33582246xxx, fax number: +33582246xxx.