Reviewer's report 
 Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting Title: 
enzyme (ACE) gene with tropical calcific pancreatitis 
 1  13 September 2006 Version: Date: 
 cedric le marechal Reviewer: 
Reviewer's report: 
General 
The work presented by Bhaskar et al. is a case-control study that aims to evaluate the association of the 
ACE gene Ins/Del polymorphism in a population from india that suffers of Tropical Chronic Pancreatitis 
(TCP) or Fibro-Calculous Pancreatic Diabetes (FCPD). This is a replicate of the work published by Oruc et 
al (JOP 2004;5(6):457-463) that was the first to investigate, at the genetic level, the association between the 
ACE gene and chronic pancreatitis. 
These two works are in accordance to discard any association between ACE-Ins/del and chronic 
pancreatitis. Nevertheless, the work from Bhaskar et al. is original concerning the phenotype (TCP/FCPD is 
encountered only in the tropical region), and the genetic background of the studied population highlighted by 
the very high incidence of the p.N34S variant of SPINK1 gene (#50%) compared to the 10 to 25% in the 
caucasian patients. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
1) The original study from Oruc et al. (#ref 26) does not appear in the text till it is mentionned at the 
beginning of the last paragraph of the discussion section. It seems to be necessary to mention the first work 
that generated the hypothesis in the background section of the abstract and text. 
2) In the Methods section - Genetic analysis part : 
The analysis conditions have to be more accurately described concerning the design of the primers. Providing the sequence of the primers or a reference would allow to replicate the experiment. Are the 
primers outside of the Ins/del or do they pinpoint the insertion junction ? these precision should clarify the 
reader about the "Ambiguity" in the genotyping results that are noted. If the primers are outside, the size difference between Ins to Del genotype is 287nt !! Can you precise the criterias that led you to select the 10% samples that were confirmed by sequencing 
(randomly ?). 
------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting Title: 
enzyme (ACE) gene with tropical calcific pancreatitis 
 1  13 September 2006 Version: Date: 
 cedric le marechal Reviewer: 
Reviewer's report: 
General 
The work presented by Bhaskar et al. is a case-control study that aims to evaluate the association of the 
ACE gene Ins/Del polymorphism in a population from india that suffers of Tropical Chronic Pancreatitis 
(TCP) or Fibro-Calculous Pancreatic Diabetes (FCPD). This is a replicate of the work published by Oruc et 
al (JOP 2004;5(6):457-463) that was the first to investigate, at the genetic level, the association between the 
ACE gene and chronic pancreatitis. 
These two works are in accordance to discard any association between ACE-Ins/del and chronic 
pancreatitis. Nevertheless, the work from Bhaskar et al. is original concerning the phenotype (TCP/FCPD is 
encountered only in the tropical region), and the genetic background of the studied population highlighted by 
the very high incidence of the p.N34S variant of SPINK1 gene (#50%) compared to the 10 to 25% in the 
caucasian patients. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
1) The original study from Oruc et al. (#ref 26) does not appear in the text till it is mentionned at the 
beginning of the last paragraph of the discussion section. It seems to be necessary to mention the first work 
that generated the hypothesis in the background section of the abstract and text. 
2) In the Methods section - Genetic analysis part : 
The analysis conditions have to be more accurately described concerning the design of the primers. Providing the sequence of the primers or a reference would allow to replicate the experiment. Are the 
primers outside of the Ins/del or do they pinpoint the insertion junction ? these precision should clarify the 
reader about the "Ambiguity" in the genotyping results that are noted. If the primers are outside, the size difference between Ins to Del genotype is 287nt !! Can you precise the criterias that led you to select the 10% samples that were confirmed by sequencing 
(randomly ?). 
------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting Title: 
enzyme (ACE) gene with tropical calcific pancreatitis 
 1  13 September 2006 Version: Date: 
 cedric le marechal Reviewer: 
Reviewer's report: 
General 
The work presented by Bhaskar et al. is a case-control study that aims to evaluate the association of the 
ACE gene Ins/Del polymorphism in a population from india that suffers of Tropical Chronic Pancreatitis 
(TCP) or Fibro-Calculous Pancreatic Diabetes (FCPD). This is a replicate of the work published by Oruc et 
al (JOP 2004;5(6):457-463) that was the first to investigate, at the genetic level, the association between the 
ACE gene and chronic pancreatitis. 
These two works are in accordance to discard any association between ACE-Ins/del and chronic 
pancreatitis. Nevertheless, the work from Bhaskar et al. is original concerning the phenotype (TCP/FCPD is 
encountered only in the tropical region), and the genetic background of the studied population highlighted by 
the very high incidence of the p.N34S variant of SPINK1 gene (#50%) compared to the 10 to 25% in the 
caucasian patients. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
1) The original study from Oruc et al. (#ref 26) does not appear in the text till it is mentionned at the 
beginning of the last paragraph of the discussion section. It seems to be necessary to mention the first work 
that generated the hypothesis in the background section of the abstract and text. 
2) In the Methods section - Genetic analysis part : 
The analysis conditions have to be more accurately described concerning the design of the primers. Providing the sequence of the primers or a reference would allow to replicate the experiment. Are the 
primers outside of the Ins/del or do they pinpoint the insertion junction ? these precision should clarify the 
reader about the "Ambiguity" in the genotyping results that are noted. If the primers are outside, the size difference between Ins to Del genotype is 287nt !! Can you precise the criterias that led you to select the 10% samples that were confirmed by sequencing 
(randomly ?). 
------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant