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Objectives: The aim of this study was to evaluate whether variations in the glycoprotein 2 gene (GP2) may potentially affect the risk of chronic pancreatitis., Methods: Six hundred sixty-one French white patients (idiopathic chronic pancreatitis, n = 590; familial chronic pancreatitis, n = 42; hereditary pancreatitis, n = 29), 445 Dravidian patients from India (tropical calcific pancreatitis, n = 306; idiopathic chronic pancreatitis, n = 139), and 962 unrelated healthy subjects (French white, n = 500; Dravidian, n = 462) participated in this case-control association study. The entire coding sequence of the GP2 gene was searched for conventional genetic variations by direct sequencing, whereas all 12 exons of the GP2 gene were screened for copy number variations by quantitative fluorescent multiplex-polymerase chain reaction., Results: Only 3 rare missense mutations (p.A137T, p.E250D, and p.V432M; only p.E250D was not detected in any control subjects) and 3 common synonymous polymorphisms (c.348C>T, c.714G>C, and c.1275A>G) were identified. The c.348C>T and c.1275A>G variations were found to be contradictorily associated with the disease (ranging from protective effects to disease-predisposing effects) in the French white and Indian populations., Conclusion: The paucity of patient-specific missense mutations and contradictory findings with respect to 2 common polymorphisms in the 2 contrasting populations suggest that the GP2 gene is unlikely to play a major role in the etiology of chronic pancreatitis.

Background & Aims: We have recently reported that the triplication of a approximately 605 kilobase segment containing the PRSS1 (encoding cationic trypsinogen) and PRSS2 (encoding anionic trypsinogen) genes causes hereditary pancreatitis. Here we went further to investigate whether this copy number mutation could account for some unidentified French white patients with idiopathic chronic pancreatitis (ICP) or familial chronic pancreatitis (FCP) as well as Indian patients with tropical calcific pancreatitis (TCP)., Methods: Patients and controls were screened by means of previously described quantitative fluorescent multiplex polymerase chain reaction and/or genotyping of the microsatellite marker rs3222967., Results: The approximately 605 kilobase triplication and a novel duplication (confirmed by fluorescence in situ hybridization) of the trypsinogen locus were detected in 10 and 2 of 202 ICP patients, respectively (age of disease onset, 20 years. However, the 2 trypsinogen copy number mutations were observed in neither 103 FCP patients nor 268 Indian TCP patients., Conclusions: Our findings revealed the molecular basis of 6% of the young ICP patients and further demonstrated that chronic pancreatitis is a genomic disorder. Our findings also add to the mounting evidence showing that trypsinogen gene mutations do not appear to play an important role in the pathogenesis of TCP in the Indian population. Finally, a dividend of this study is that we have provided convincing evidence to show that all 5 previously described copy number variations involving PRSS1 or/and PRSS2 are artifacts.