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.
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.
Authors: Anish Kolly; C Shivaprasad; Annie A Pulikkal; Sridevi Atluri; Vijaya Sarathi; C S Dwarakanath Journal: Indian J Endocrinol Metab Date: 2017 Jul-Aug