Reviewer's report
Title:Toll-like receptor 4 Asp299Gly, Thr399Ile polymorphisms in Moroccan
patients with inflammatory bowel disease
Version:1Date:8 July 2014
Reviewer: Javier Martin
Reviewer's report:
In this manuscript, the authors first analyzed two polymorphisms, Asp299Gly and
Thr399Ile at the TLR4 gene, in a Moroccan IBD cohort. They found no
association of these SNPs with Crohn’s disease (CD) or ulcerative colitis (UC). In
a second part, they performed a meta-analysis for the Asp299Gly genetic variant
including data from previous studies. This combined analysis evidenced an
association of this SNP with CD, but not with UC. Some important points should
be considered by the authors.
Major
1. There are several studies in the literature analyzing the role of both Asp299Gly
and Thr399Ile in the IBD susceptibility. Taking this into account, why the authors
did not perform a meta-analysis for the Thr399Ile polymorphism?, mainly
considering that a meta-analysis evaluating the role of Asp299Gly, but not of
Thr399Ile, in IBD has already been published. For the Thr399Ile SNP, a
combined analysis of the present data and those from previous studies should be
included in the manuscript.
2. Given the low statistical power of the case/control analysis, the most important
results of the present study are those derived from the meta-analysis. In my
opinion, the discussion should be focused on the results of these pooled
analyses. In addition, these results should be included in the abstract of the new
version of the manuscript.
3. It is known that a number of genetic risk factors are shared between CD and
UC. Indeed, associations between the Asp299Gly and Thr399Ile genetic variants
and both diseases have been found in several studies. From this point of view, it
would be interesting to perform a meta-analysis combining CD and UC patients
for the two tested SNPs.
4. In the last paragraph of the results section authors stated: “Noteworthy, there
was a higher percentage of mutated allele coexistence in Crohn’s disease
patients compared to ulcerative colitis or healthy controls, suggesting that
mutated allele coexistence might increase susceptibility to CD”. Was a haplotype
analysis performed? The results of this analysis should be included in the
manuscript.
Minor
1. TLR4 should be written in italics when referring to the gene
2. Some references about the epidemiology and etiopathogenesis of IBD should
be included in the first paragraph of the introduction.
3. The introduction, results, and discussion sections, should be reorganized.
Paragraphs relating to the same subject should not be separated by full stop.
4. In Tables 1 and 2, Asp299Gly is mistyped.
5. The abbreviations of Crohn’s disease, CD, and ulcerative colitis, UC, should
be indicated when these terms are used for the first time (in the study population
section). Then, abbreviations should be used through the manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I have no competing interest
Reviewer's report
Title:Toll-like receptor 4 Asp299Gly, Thr399Ile polymorphisms in Moroccan
patients with inflammatory bowel disease
Version:1Date:8 July 2014
Reviewer: Javier Martin
Reviewer's report:
In this manuscript, the authors first analyzed two polymorphisms, Asp299Gly and
Thr399Ile at the TLR4 gene, in a Moroccan IBD cohort. They found no
association of these SNPs with Crohn’s disease (CD) or ulcerative colitis (UC). In
a second part, they performed a meta-analysis for the Asp299Gly genetic variant
including data from previous studies. This combined analysis evidenced an
association of this SNP with CD, but not with UC. Some important points should
be considered by the authors.
Major
1. There are several studies in the literature analyzing the role of both Asp299Gly
and Thr399Ile in the IBD susceptibility. Taking this into account, why the authors
did not perform a meta-analysis for the Thr399Ile polymorphism?, mainly
considering that a meta-analysis evaluating the role of Asp299Gly, but not of
Thr399Ile, in IBD has already been published. For the Thr399Ile SNP, a
combined analysis of the present data and those from previous studies should be
included in the manuscript.
2. Given the low statistical power of the case/control analysis, the most important
results of the present study are those derived from the meta-analysis. In my
opinion, the discussion should be focused on the results of these pooled
analyses. In addition, these results should be included in the abstract of the new
version of the manuscript.
3. It is known that a number of genetic risk factors are shared between CD and
UC. Indeed, associations between the Asp299Gly and Thr399Ile genetic variants
and both diseases have been found in several studies. From this point of view, it
would be interesting to perform a meta-analysis combining CD and UC patients
for the two tested SNPs.
4. In the last paragraph of the results section authors stated: “Noteworthy, there
was a higher percentage of mutated allele coexistence in Crohn’s disease
patients compared to ulcerative colitis or healthy controls, suggesting that
mutated allele coexistence might increase susceptibility to CD”. Was a haplotype
analysis performed? The results of this analysis should be included in the
manuscript.
Minor
1. TLR4 should be written in italics when referring to the gene
2. Some references about the epidemiology and etiopathogenesis of IBD should
be included in the first paragraph of the introduction.
3. The introduction, results, and discussion sections, should be reorganized.
Paragraphs relating to the same subject should not be separated by full stop.
4. In Tables 1 and 2, Asp299Gly is mistyped.
5. The abbreviations of Crohn’s disease, CD, and ulcerative colitis, UC, should
be indicated when these terms are used for the first time (in the study population
section). Then, abbreviations should be used through the manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I have no competing interest
Please review this paper.
user
Reviewer's report
Title:Toll-like receptor 4 Asp299Gly, Thr399Ile polymorphisms in Moroccan
patients with inflammatory bowel disease
Version:1Date:8 July 2014
Reviewer: Javier Martin
Reviewer's report:
In this manuscript, the authors first analyzed two polymorphisms, Asp299Gly and
Thr399Ile at the TLR4 gene, in a Moroccan IBD cohort. They found no
association of these SNPs with Crohn’s disease (CD) or ulcerative colitis (UC). In
a second part, they performed a meta-analysis for the Asp299Gly genetic variant
including data from previous studies. This combined analysis evidenced an
association of this SNP with CD, but not with UC. Some important points should
be considered by the authors.
Major
1. There are several studies in the literature analyzing the role of both Asp299Gly
and Thr399Ile in the IBD susceptibility. Taking this into account, why the authors
did not perform a meta-analysis for the Thr399Ile polymorphism?, mainly
considering that a meta-analysis evaluating the role of Asp299Gly, but not of
Thr399Ile, in IBD has already been published. For the Thr399Ile SNP, a
combined analysis of the present data and those from previous studies should be
included in the manuscript.
2. Given the low statistical power of the case/control analysis, the most important
results of the present study are those derived from the meta-analysis. In my
opinion, the discussion should be focused on the results of these pooled
analyses. In addition, these results should be included in the abstract of the new
version of the manuscript.
3. It is known that a number of genetic risk factors are shared between CD and
UC. Indeed, associations between the Asp299Gly and Thr399Ile genetic variants
and both diseases have been found in several studies. From this point of view, it
would be interesting to perform a meta-analysis combining CD and UC patients
for the two tested SNPs.
4. In the last paragraph of the results section authors stated: “Noteworthy, there
was a higher percentage of mutated allele coexistence in Crohn’s disease
patients compared to ulcerative colitis or healthy controls, suggesting that
mutated allele coexistence might increase susceptibility to CD”. Was a haplotype
analysis performed? The results of this analysis should be included in the
manuscript.
Minor
1. TLR4 should be written in italics when referring to the gene
2. Some references about the epidemiology and etiopathogenesis of IBD should
be included in the first paragraph of the introduction.
3. The introduction, results, and discussion sections, should be reorganized.
Paragraphs relating to the same subject should not be separated by full stop.
4. In Tables 1 and 2, Asp299Gly is mistyped.
5. The abbreviations of Crohn’s disease, CD, and ulcerative colitis, UC, should
be indicated when these terms are used for the first time (in the study population
section). Then, abbreviations should be used through the manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I have no competing interest
assistant