Example of letter to Editor …………………………………………………… ……………………………………………………. Faculty of Medicine, Khon Kaen University Khon Kaen 40002, Thailand Tel / Fax 66-43-……………… Email: …………………… Date Prof. Prof. Michel Eichelbaum (Name of the Editor) Pharmacogenetics and Genomics (Name of the Journal) Subject : Manuscript submission Dear Prof. Michel Eichelbaum I would like to submit the manuscript entitled "Strong association between HLA-B*5801 and allopurinol -induced Stevens- Johnson Syndrome and toxic epidermal necrolysis in a Thai population". A strong association between allopurinolinduced SCAR and HLA-B*5801 has been reported in a Han Chinese population, however only a moderate association was observed in European and Japanese populations. The issue of ethnic difference in the association of HLA gene and severe cautaneous reactions have been raised for several drugs (i.e. carbamazepine, abacavir). In the present study, we demonstrated in a Thai population that the risk of allopurinolinduced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared with those that did not carry this allele, with an odds ratio of 348.3. The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinolinduced SJS/TEN were 100% and 87%, respectively. Our results suggest that HLAB*5801 may be a sensitive genetic marker for screening Thai individuals that may be at risk for allopurinol-induced life-threatening SJS and TEN. I warrant that this manuscript has been read by all co-authors and I have submitted this manuscript on behalf of all the authors with their full consent. I would be very appreciated if you could consider our manuscript for publication in your journal. Sincerely Yours, (Dr………………………………………..) Letter to editor after manuscript has been accepted ……………………………………………… ……………………………………………… Faculty of Medicine, Khon Kaen University Khon Kaen 40002, Thailand Tel / Fax 66-43-348397 Email: wichitt@kku.ac.th 7 July 2009 Prof. Michel Eichelbaum Pharmacogenetics and Genomics Subject : Revised manuscript submission (PGEN-2009-107) Dear Prof. Michel Eichelbaum, Thank you very much for considering our manuscript entitled "Strong association between HLA-B*5801 and allopurinol -induced Stevens- Johnson Syndrome and toxic epidermal necrolysis in a Thai population (PGEN-2009-107)” to be published in your journal. We have revised the manuscript according to the reviewers’ comments. We would be very appreciated if you could consider our manuscript to publish as original article in your journal. Sincerely Yours, (Dr. ………………………….) Response to Reviewers Reviewer #1: This study investigated the association in a Thai population between allopurino-induced SJS/TEN and HLA-B*5801 which was reported to have a strong correlation with allopurinol-induced SCAR in Han Chinese. This is the first report that the extremely strong association between the allele and allopurinol-induced SJS/TEN was observed in other ethnic groups than Han Chinese. However, maybe, it appears too redundant and could be shortened. Introduction, Discussion and citations from literatures appear too long and Table 3 can be deleted. The reviewer feels that it is suitable to publish the manuscript as a Short Communication. Response: Thank you very much for valuable comments. We did revised and shortened the manuscript as suggested. The introduction, results, discussion and citations have been revised to avoid the redundancy. We still what to keep Table 3 because it could give all the detail of the genes that we investigated. We would like to ask the reviewer to consider our manuscript as original article instead of the short communication. Reviewer #2: This article shows that HLA-B*5801 is as highly positive in patients of allopurinol-induced SJS and TEN in Thai population as in Han Chinese population, too. As for drug reactions-HLA relationship, there are regional/ethnic discrepancies and the impact of HLA-type for pathogenesis is still controversial. Therefore, this paper will provide new information and will be appropriate for publication in Pharmacogenomics. Minor comment: Do you have information of HLA-A type of the patients, especially A*3303? Response: Thank you for accepting our manuscript for publication. We did not have any information on HLA-A genotypes of the studied population since it has been reported in Han Chinese that the association between HLA-A*3303 and allopurinol-induced SJS/TEN the association was much weaker than those found with the HLA-B*5801{Hung, 2005 #71}. Therefore, we haven’t analyzed the HLA-A genotypes in our studied population.