6.5 The Common CTRC Synonymous Variant（c1.80C＞T）In...
Based on a review of clinical studies，Yadav and colleagues concluded that approximately 1/3 of patients with acute pancreatitis will develop recurrent acute pancreatitis（RAP）and approximately 1/3 of RAP patients will develop chronic pancreatitis（Yadav 2011；Yadav et al.2012；Yadav and Lowenfels 2013）.Patients with hereditary pancreatitis and those with a predisposing environmental factor such as alcohol abuse and smoking have the highest progression rate.
LaRush and co-workers evaluated the occurrence of CTRC variants in a total of 694 patients with chronic pancreatitis，448 patients with RAP，and 1017 controls from the North American Pancreatitis Study 11 cohort（LaRusch et al.2015）.They detected rare CTRC variants such as p.Ala73Thr and p.Arg254Trp in the chronic pancreatitis and/or RAP patients but the low detection rate and small sample sizes prevented them from obtaining a significant association.However，they found that the common synonymous variant，c.180C＞T，was significantly associated with chronic pancreatitis but not RAP（LaRusch et al.2015）.The c.180C＞T variant had been previously reported to be overrepresented in a small cohort（N=42）of French patients with familial chronic pancreatitis（Masson et al.2008b）and Indian patients with tropical chronic pancreatitis（Derikx et al.2009；Paliwal et al.2013）.(https://www.daowen.com)
The important message emanating from the finding of an association of the CTRC c.180C＞T variant with chronic pancreatitis but not RAP is that loss of CTRC function accelerates progression from RAP to chronic pancreatitis（LaRusch et al.2015）.The c.180C＞T variant was also found to be significantly associated with CFTR or SPINK1 variants，alcohol and smoking，suggesting the involvement of complex geneticgenetic and genetic-environmental interactions in driving the rapid disease progression（LaRusch et al.2015）.These findings notwithstanding，whether the CTRC c.180C＞T variant is itself functional or whether it instead represents a linkage disequilibrium marker，remains to be clarified.