Reviewer's report
Title:Combined effect of regulatory polymorphisms on transcription of UGT1A1
as a cause of Gilbert syndrome
Version: 2Date:10 December 2009
Reviewer: Shinichi Ikushiro
Reviewer's report:
General comment
The authers described the combined effect of regulatory region polymorphisms of
Glibert syndrome on UGT1A1 promoter-dependent transcriptional activity. It is
important to estimate transcriptional activity of UGT1A1 gene in individual for
estimation of side effects of several drug treatment ( eg. irrinotecan toxicity). The
paper reported several haplotypes with different combinations of the 14 relavant
mutations of UGT1A1 expression regulatory region in Gilbert syndrome. Although
this article indicates the combine effects of polymorphisms in ( TATA box and
related regions), it is difficult to find the significant difference of expression
efficiency in those mutations.
Specific comments
1) To estimate the effect of CAR on the promoter –dependent expression in
reporter assay system, normalization of CAR expression is needed. . Did you
check the expression level of CAR in each experiments.
2) It is difficult to find the use of supplemental data in text. You should more
describe about the result of supplement data for multiple regression analysis.
3) Reference list contains some mistake. You should carefully check the
reference in Ref.23 and 30.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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:10 December 2009
Reviewer: Shinichi Ikushiro
Reviewer's report:
General comment
The authers described the combined effect of regulatory region polymorphisms of
Glibert syndrome on UGT1A1 promoter-dependent transcriptional activity. It is
important to estimate transcriptional activity of UGT1A1 gene in individual for
estimation of side effects of several drug treatment ( eg. irrinotecan toxicity). The
paper reported several haplotypes with different combinations of the 14 relavant
mutations of UGT1A1 expression regulatory region in Gilbert syndrome. Although
this article indicates the combine effects of polymorphisms in ( TATA box and
related regions), it is difficult to find the significant difference of expression
efficiency in those mutations.
Specific comments
1) To estimate the effect of CAR on the promoter –dependent expression in
reporter assay system, normalization of CAR expression is needed. . Did you
check the expression level of CAR in each experiments.
2) It is difficult to find the use of supplemental data in text. You should more
describe about the result of supplement data for multiple regression analysis.
3) Reference list contains some mistake. You should carefully check the
reference in Ref.23 and 30.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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:10 December 2009
Reviewer: Shinichi Ikushiro
Reviewer's report:
General comment
The authers described the combined effect of regulatory region polymorphisms of
Glibert syndrome on UGT1A1 promoter-dependent transcriptional activity. It is
important to estimate transcriptional activity of UGT1A1 gene in individual for
estimation of side effects of several drug treatment ( eg. irrinotecan toxicity). The
paper reported several haplotypes with different combinations of the 14 relavant
mutations of UGT1A1 expression regulatory region in Gilbert syndrome. Although
this article indicates the combine effects of polymorphisms in ( TATA box and
related regions), it is difficult to find the significant difference of expression
efficiency in those mutations.
Specific comments
1) To estimate the effect of CAR on the promoter –dependent expression in
reporter assay system, normalization of CAR expression is needed. . Did you
check the expression level of CAR in each experiments.
2) It is difficult to find the use of supplemental data in text. You should more
describe about the result of supplement data for multiple regression analysis.
3) Reference list contains some mistake. You should carefully check the
reference in Ref.23 and 30.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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
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