CTRC Genetic Variants, Including c.180TT, are Strongly Associated With Chronic Pancreatitis in Paediatric Patients

ABSTRACTGenetic studies in adults/adolescent patients with chronic pancreatitis (CP) identified chymotrypsinogen C (CTRC) genetic variants but their association with CP risk have been difficult to replicate. OBJECTIVE:To evaluate the risk of CP associated with CTRC variants in CP paediatric patients-control study. DESIGN:The distribution of CTRC variants in CP paediatric cohort (n = 136, median age at CP onset 8 years) with no history of alcohol/smoking abuse was compared to controls (n = 401, median age 45). RESULTS:We showed that p.Arg254Trp (4.6%) and p.Lys247_Arg254del (5.3%) heterozygous mutations are frequent and significantly associated with CP risk in paediatric patients (OR = 19.1; 95%CL:2.8–160; P = 0.001 and OR = 5.5; 95%CL:1.6–19.4; P = 0.001, respectively). For the first time, we demonstrated that the c.180TT genotype of common p.Gly60Gly variant is strong, an independent CP risk factor (OR = 23; 95%CL:7.7–70; P A variant, both CA and AA genotype, is significantly underrepresented in CP compared to controls (15% vs. 35%; OR = 0.33; 95% CL:0.19–0.59; P A variant may play a protective role against CP development.