Review for 10.1186/1471-230X-6-42 (2006)

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  11 September 2006 Version: Date: 
 Atsushi Masamune Reviewer: 
Reviewer's report: 
General 
In this study, Bhaskar et al. examined the association of an insertion/deletion (I/D) polymorphism in the ACE 
gene with TCP or FCPD. They showed that there was no significant association between this I/D 
polymorphism and TCP or FCPD. The authors concluded that this I/D polymorphism did not play a role in 
the pathogenesis and progression of TCP. This is an interesting study because TCP and FCPD are unique 
entities of CP with different genetic background. Most of the gastroenterologists except for those working in 
the tropical region do not have an access to patients with TCP or FCPD. However, I have some suggestions 
to further increase the quality of this study. 
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Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 1. It has been previously shown that this I/D polymorphism did not alter susceptibility to chronic pancreatits 
(CP) (ref. # 26). The originality of this study depends on the fact that the authors examined the association 
of this polymorphism with TCP and FCPD. It is disappointing that the authors merely compared the 
association based on the presence (FCPD) or absence (TCP) of diabetes mellitus. The reviewer suggests that the authors should examine the association of this polymorphism with clinical features of CP including 
symptom onset and imaging findings (calcification, pseudocyst, and MPD abnormalities). 
2. The definition of “progression” of TCP is unclear. It appears that the authors merely define TCP patients 
with diabetes as FCPD, and patients without diabetes as TCP. In general, the term “progression” implies not 
only diabetes but also other phenotypes such as endocrine insufficiency. Although the reviewer agrees that 
FCPD might be a progressive form of TCP, the authors should present some clinical indicators of 
“progression” in patients. Of note, patients with FCPD presented symptoms later than those with TCP. If FCPD is a merely progressive form of TCP, the age of symptom onset should be similar. 
3. The experimental procedure is too brief. It is difficult for readers to reproduce this study. For example, the 
primer sequences as well as the reaction condition of the PCR are missing. The representative agarose-gel
electrophoresis of the PCR (showing each genotype) should be presented. 4. It is unclear whether the patients were heterozygous or homozygous for the N34S mutation in the SPINK1 gene. 
5. The authors should describe the respective p-values for each comparison to show that there was no 
statistical significance. 6. The description in the last paragraph in the page 7 is inaccurate. The previous study (ref #26) deals with familial and sporadic CP, not idiopathic CP. 
7. In the abstract, the authors state that the deletion does not show any significant association with the 
fibrosis of TCP and FCPD. However, no data were presented as to the occurrence of fibrosis. 
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Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
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Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests.