Reviewer's report
Title:Combined effect of regulatory polymorphisms on transcription of UGT1A1
as a cause of Gilbert syndrome
Version: 2Date:5 February 2010
Reviewer: Rene HM te Morsche
Reviewer's report:
In the report by Katsuyuki Matsui and coworkers the promoter region of a number
of Japanese and Caucasian patients and controls were sequenced. Using the
most common haplotypes found they constructed luciferase containing plasmids
to reveal how much each haplotype contributes to the transcription of UGT1A1.
This report gives interesting information about what regions of the promoter are
important and how they influence the transcription of UGT1A1.
Minor Essential Revisions
Results:
Constructing diplotypes of the patients and controls would be really interesting.
Are patients always homozygous for certain polymorphisms in contrast to
controls?
And if the author have access to the bilirubin levels of the subjects used in this
report these would be very helpful in relating them to the diplotypes and the
transcription activity.
Discussion:
“Our result are also consistent…..Gilbert syndrome (5-10% of the population)”
This statement is not accurate since Gilbert syndrome is believed to be
associated with homozygous A(TA)7TAA. The prevalence of homozygous
subjects is about 12% in Caucasians and thus is not that different.
“Our result for A(TA)7TAA …..c.-3275T>G but without A(TA)7TAA”. However
also a haplotype with c.-3275G (typeII) was found in 23 controls in contrast to the
haplotypes with A(TA)7TAA which is less frequent found in controls. This
implicates that the c.3275T>G polymorphism is less important in Gilbert
syndrome patients than the A(TA)6/7TAA polymorphism although the reduction
in transcription is higher. Could the authors explain this.
Discretionary revisions
Background:
There are some articles like the one from Katrin Borucki et al. 2009 where
bilirubin levels are related to some polymorphisms also mentioned in this report.
To mention some of these findings would be of surplus value why the
researchers in this report constructed the plasmids in order to measure
transcription activity.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Combined effect of regulatory polymorphisms on transcription of UGT1A1
as a cause of Gilbert syndrome
Version: 2Date:5 February 2010
Reviewer: Rene HM te Morsche
Reviewer's report:
In the report by Katsuyuki Matsui and coworkers the promoter region of a number
of Japanese and Caucasian patients and controls were sequenced. Using the
most common haplotypes found they constructed luciferase containing plasmids
to reveal how much each haplotype contributes to the transcription of UGT1A1.
This report gives interesting information about what regions of the promoter are
important and how they influence the transcription of UGT1A1.
Minor Essential Revisions
Results:
Constructing diplotypes of the patients and controls would be really interesting.
Are patients always homozygous for certain polymorphisms in contrast to
controls?
And if the author have access to the bilirubin levels of the subjects used in this
report these would be very helpful in relating them to the diplotypes and the
transcription activity.
Discussion:
“Our result are also consistent…..Gilbert syndrome (5-10% of the population)”
This statement is not accurate since Gilbert syndrome is believed to be
associated with homozygous A(TA)7TAA. The prevalence of homozygous
subjects is about 12% in Caucasians and thus is not that different.
“Our result for A(TA)7TAA …..c.-3275T>G but without A(TA)7TAA”. However
also a haplotype with c.-3275G (typeII) was found in 23 controls in contrast to the
haplotypes with A(TA)7TAA which is less frequent found in controls. This
implicates that the c.3275T>G polymorphism is less important in Gilbert
syndrome patients than the A(TA)6/7TAA polymorphism although the reduction
in transcription is higher. Could the authors explain this.
Discretionary revisions
Background:
There are some articles like the one from Katrin Borucki et al. 2009 where
bilirubin levels are related to some polymorphisms also mentioned in this report.
To mention some of these findings would be of surplus value why the
researchers in this report constructed the plasmids in order to measure
transcription activity.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Combined effect of regulatory polymorphisms on transcription of UGT1A1
as a cause of Gilbert syndrome
Version: 2Date:5 February 2010
Reviewer: Rene HM te Morsche
Reviewer's report:
In the report by Katsuyuki Matsui and coworkers the promoter region of a number
of Japanese and Caucasian patients and controls were sequenced. Using the
most common haplotypes found they constructed luciferase containing plasmids
to reveal how much each haplotype contributes to the transcription of UGT1A1.
This report gives interesting information about what regions of the promoter are
important and how they influence the transcription of UGT1A1.
Minor Essential Revisions
Results:
Constructing diplotypes of the patients and controls would be really interesting.
Are patients always homozygous for certain polymorphisms in contrast to
controls?
And if the author have access to the bilirubin levels of the subjects used in this
report these would be very helpful in relating them to the diplotypes and the
transcription activity.
Discussion:
“Our result are also consistent…..Gilbert syndrome (5-10% of the population)”
This statement is not accurate since Gilbert syndrome is believed to be
associated with homozygous A(TA)7TAA. The prevalence of homozygous
subjects is about 12% in Caucasians and thus is not that different.
“Our result for A(TA)7TAA …..c.-3275T>G but without A(TA)7TAA”. However
also a haplotype with c.-3275G (typeII) was found in 23 controls in contrast to the
haplotypes with A(TA)7TAA which is less frequent found in controls. This
implicates that the c.3275T>G polymorphism is less important in Gilbert
syndrome patients than the A(TA)6/7TAA polymorphism although the reduction
in transcription is higher. Could the authors explain this.
Discretionary revisions
Background:
There are some articles like the one from Katrin Borucki et al. 2009 where
bilirubin levels are related to some polymorphisms also mentioned in this report.
To mention some of these findings would be of surplus value why the
researchers in this report constructed the plasmids in order to measure
transcription activity.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
assistant