Dear editorial board of Cerebrovascular Diseases,

Please find enclosed the manuscript: Association of a SNP in the ALOX5AP gene with risk of Ischemic Stroke, by Sarah H., et al., to be submitted as a Original Research Article to Cerebrovascular Diseases for consideration of publication. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication.

In this manuscript, we report the results of the first study on the genetic and functional roles of the ALOX5AP and PDE4D genes on the risk of suffering an ischemic stroke in the French population. We believe that our findings could be of interest to the readers of Cerebrovascular Diseases because they bring new light on the controversial role of the ALOX5AP and PDE4D genes in stroke and replicate some of the results observed by Helgadottir et al. in an Icelandic population and published in Nature Genetics in 2004. Indeed, we demonstrate an association resistant to Bonferroni of the SG13S114 (rs10507391) T allele of the ALOX5AP gene with an increased risk of ischemic stroke in white populations through an actualized meta-analysis, and in the never tested before Iberian population through case-control study. Moreover, we investigated and showed for the first time that ALOX5AP mRNA levels depended on the SG13S114 genotypes and stroke patients had higher ALOX5AP mRNA levels than healthy controls. These results thus support a role for the ALOX5AP gene in stroke and uncover diagnostic and therapeutic expectations.

We hope that the editorial board will agree on the interest of this study.

Sincerely yours,

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

Corresponding author: Lucas D. at Stroke Laboratory, Marie Curie Research Institute, 75000, Paris, France, xxx@mariecurie.fr, phone number: +33582246xxx, fax number: +33582246xxx.