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Background  Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to developing countries in tropical regions and one of its important features is invariable progression to diabetes, a condition called fibro-calculous pancreatic diabetes (FCPD), but the nature of diabetes in TCP is controversial. We analysed the recently reported type 2 diabetes (T2D) associated polymorphisms in the  TCF7L2  gene using a case-control approach, under the hypothesis that  TCF7L2  variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the  TCF7L2  variants and N34S  SPINK1  and L26V  CTSB  mutations, since they are strong predictors of risk for TCP.    Methods  Two polymorphisms rs7903146 and rs12255372 in the  TCF7L2  gene were analyzed by direct sequencing in 478 well-characterized TCP patients and 661 healthy controls of Dravidian and Indo-European ethnicities. Their association with TCP with diabetes (FCPD) and without diabetes was tested in both populations independently using chi-square test. Finally, a meta analysis was performed on all the cases and controls for assessing the overall significance irrespective of ethnicity. We dichotomized the whole cohort based on the presence or absence of N34S  SPINK1  and L26V  CTSB  mutations and further subdivided them into TCP and FCPD patients and compared the distribution of  TCF7L2  variants between them.    Results  The allelic and genotypic frequencies for both  TCF7L2  polymorphisms, did not differ significantly between TCP patients and controls belonging to either of the ethnic groups or taken together. No statistically significant association of the SNPs was observed with TCP or FCPD or between carriers and non-carriers of N34S  SPINK1  and L26V  CTSB  mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S  SPINK1  variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93–2.70, P = 0.09), while,  TCF7L2 variant showed a statistically significant association between TCP and FCPD patients carrying the 26V allele (OR = 1.69, 95% CI = 1.11–2.56, P = 0.013).    Conclusion  Type 2 diabetes associated  TCF7L2  variants are not associated with diabetes in TCP. Since,  TCF7L2  is a major susceptibility gene for T2D, it may be hypothesized that the diabetes in TCP patients may not be similar to T2D. Our data also suggests that co-existence of  TCF7L2  variants and the  SPINK1  and  CTSB  mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.

bmc medical genetics

TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSBmutations in predicting diabetes