Reviewer's report
Title:The I148M PNPLA3 polymorphism influences serum adiponectin in an
association study in patients with fatty liver and healthy controls
Version: 1Date:30 March 2012
Reviewer: Stefano Romeo
Reviewer's report:
The manuscript by Valenti et al. proposes the association of the PNPLA3 I148M
with adiponectin levels in individuals with NAFLD but not with CHC. The study is
well written and it proposes an interesting new association of the PNPLA3 I148M
genetic variants. I think it is an important piece of information in the field and
deserves publications after minor changes.
Specific comments:
1. Adiponectin levels are known to be inversely correlated with the degree of
insulin resistance. I am somewhat surprised by the fact that, despite authors find
an association between lower adiponectin levels and the 148M allele, they do not
see any difference in the insulin sensitivity (assessed by HOMA-IR and fasting
insulin levels). I have noticed that, while adiponectin was log transformed before
entering the analyses, HOMA-IR and fasting insulin were not. These two
variables are highly skewed so they should also be log transformed and showed
as median and interquartile range. I would suggest to carry out the analyses on
HOMA-IR and fasting insulin levels carried out in this way.
2. A recent study found an association of the PNPLA3 148M allele with insulin
resistance (Wang CW, Liver Int. 2011; 31(9):1326-31). The association authors
found in this manuscript may be compatible with this hypothesis. I would be more
careful in drawing conclusions regarding the lack of association with insulin
resistance, tone done the discussion and admit the negative association with
insulin resistance may also be due to a lack of power.
3. Authors do not find any association between the adiponectin levels and the
PNPLA3 genotype in individuals affected by chronic hepatitis. Do they have a
hypothesis on the reasons for this result? Could it be a lack of statistical power
due to a smaller effect size in the latter group due to a different gene
environment interaction? I think this should be discussed.
4. Authors should show a table with clinical characteristics, adiponectin, HOMA
IR also in CHC patients stratified by PNPLA3 I148M genotype.
5. I would not pool in NAFLD, CHC case and control groups and would not
perform a combined analysis. These are too heterogeneous groups.
6. In the mRNA analyses what were the CT values and how the arbitrary units
were calculated?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Reviewer's report
Title:The I148M PNPLA3 polymorphism influences serum adiponectin in an
association study in patients with fatty liver and healthy controls
Version: 1Date:30 March 2012
Reviewer: Stefano Romeo
Reviewer's report:
The manuscript by Valenti et al. proposes the association of the PNPLA3 I148M
with adiponectin levels in individuals with NAFLD but not with CHC. The study is
well written and it proposes an interesting new association of the PNPLA3 I148M
genetic variants. I think it is an important piece of information in the field and
deserves publications after minor changes.
Specific comments:
1. Adiponectin levels are known to be inversely correlated with the degree of
insulin resistance. I am somewhat surprised by the fact that, despite authors find
an association between lower adiponectin levels and the 148M allele, they do not
see any difference in the insulin sensitivity (assessed by HOMA-IR and fasting
insulin levels). I have noticed that, while adiponectin was log transformed before
entering the analyses, HOMA-IR and fasting insulin were not. These two
variables are highly skewed so they should also be log transformed and showed
as median and interquartile range. I would suggest to carry out the analyses on
HOMA-IR and fasting insulin levels carried out in this way.
2. A recent study found an association of the PNPLA3 148M allele with insulin
resistance (Wang CW, Liver Int. 2011; 31(9):1326-31). The association authors
found in this manuscript may be compatible with this hypothesis. I would be more
careful in drawing conclusions regarding the lack of association with insulin
resistance, tone done the discussion and admit the negative association with
insulin resistance may also be due to a lack of power.
3. Authors do not find any association between the adiponectin levels and the
PNPLA3 genotype in individuals affected by chronic hepatitis. Do they have a
hypothesis on the reasons for this result? Could it be a lack of statistical power
due to a smaller effect size in the latter group due to a different gene
environment interaction? I think this should be discussed.
4. Authors should show a table with clinical characteristics, adiponectin, HOMA
IR also in CHC patients stratified by PNPLA3 I148M genotype.
5. I would not pool in NAFLD, CHC case and control groups and would not
perform a combined analysis. These are too heterogeneous groups.
6. In the mRNA analyses what were the CT values and how the arbitrary units
were calculated?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Please review this paper.
user
Reviewer's report
Title:The I148M PNPLA3 polymorphism influences serum adiponectin in an
association study in patients with fatty liver and healthy controls
Version: 1Date:30 March 2012
Reviewer: Stefano Romeo
Reviewer's report:
The manuscript by Valenti et al. proposes the association of the PNPLA3 I148M
with adiponectin levels in individuals with NAFLD but not with CHC. The study is
well written and it proposes an interesting new association of the PNPLA3 I148M
genetic variants. I think it is an important piece of information in the field and
deserves publications after minor changes.
Specific comments:
1. Adiponectin levels are known to be inversely correlated with the degree of
insulin resistance. I am somewhat surprised by the fact that, despite authors find
an association between lower adiponectin levels and the 148M allele, they do not
see any difference in the insulin sensitivity (assessed by HOMA-IR and fasting
insulin levels). I have noticed that, while adiponectin was log transformed before
entering the analyses, HOMA-IR and fasting insulin were not. These two
variables are highly skewed so they should also be log transformed and showed
as median and interquartile range. I would suggest to carry out the analyses on
HOMA-IR and fasting insulin levels carried out in this way.
2. A recent study found an association of the PNPLA3 148M allele with insulin
resistance (Wang CW, Liver Int. 2011; 31(9):1326-31). The association authors
found in this manuscript may be compatible with this hypothesis. I would be more
careful in drawing conclusions regarding the lack of association with insulin
resistance, tone done the discussion and admit the negative association with
insulin resistance may also be due to a lack of power.
3. Authors do not find any association between the adiponectin levels and the
PNPLA3 genotype in individuals affected by chronic hepatitis. Do they have a
hypothesis on the reasons for this result? Could it be a lack of statistical power
due to a smaller effect size in the latter group due to a different gene
environment interaction? I think this should be discussed.
4. Authors should show a table with clinical characteristics, adiponectin, HOMA
IR also in CHC patients stratified by PNPLA3 I148M genotype.
5. I would not pool in NAFLD, CHC case and control groups and would not
perform a combined analysis. These are too heterogeneous groups.
6. In the mRNA analyses what were the CT values and how the arbitrary units
were calculated?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
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