OBJECTIVES: Genetic studies in adults/adolescent patients with chronic pancreatitis (CP) identified chymotrypsinogen C (CTRC) genetic variants but their association with CP risk has been difficult to replicate. To evaluate the risk of CP associated with CTRC variants in CP pediatric patients-control study. METHODS: The distribution of CTRC variants in CP pediatric cohort (n = 136, median age at CP onset 8 years) with no history of alcohol/smoking abuse was compared with 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 pediatric patients (odds ratio [OR] = 19.1; 95% CI 2.8-160; P = 0.001 and OR = 5.5; 95% CI 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% CI 7.7-70; P < 0.001) with effect size comparable to p.Arg254Trp mutation. The other novel observation is that common c.493+51C>A variant, both CA and AA genotype, is significantly underrepresented in CP compared with controls (15% vs 35%; OR = 0.33; 95% CI 0.19-0.59; P < 0.001 and 2.8% vs 11%; OR = 0.24; 95% CI 0.06-0.85; P = 0.027, respectively). CONCLUSIONS: Our study provides evidence that CTRC variants, including c.180TT (p.Gly60Gly) are strong CP risk factors. The c.493+51C>A variant may play a protective role against CP development.
OBJECTIVES: Genetic studies in adults/adolescent patients with chronic pancreatitis (CP) identified chymotrypsinogen C (CTRC) genetic variants but their association with CP risk has been difficult to replicate. To evaluate the risk of CP associated with CTRC variants in CP pediatric patients-control study. METHODS: The distribution of CTRC variants in CP pediatric cohort (n = 136, median age at CP onset 8 years) with no history of alcohol/smoking abuse was compared with 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 pediatric patients (odds ratio [OR] = 19.1; 95% CI 2.8-160; P = 0.001 and OR = 5.5; 95% CI 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% CI 7.7-70; P < 0.001) with effect size comparable to p.Arg254Trp mutation. The other novel observation is that common c.493+51C>A variant, both CA and AA genotype, is significantly underrepresented in CP compared with controls (15% vs 35%; OR = 0.33; 95% CI 0.19-0.59; P < 0.001 and 2.8% vs 11%; OR = 0.24; 95% CI 0.06-0.85; P = 0.027, respectively). CONCLUSIONS: Our study provides evidence that CTRC variants, including c.180TT (p.Gly60Gly) are strong CP risk factors. The c.493+51C>A variant may play a protective role against CP development.
Authors: Quin Y Liu; Maisam Abu-El-Haija; Sohail Z Husain; Bradley Barth; Melena Bellin; Douglas S Fishman; Steven D Freedman; Cheryl E Gariepy; Matthew J Giefer; Tanja Gonska; Melvin B Heyman; Ryan Himes; Tom K Lin; Asim Maqbool; Maria Mascarenhas; Brian A McFerron; Veronique D Morinville; Jaimie D Nathan; Chee Y Ooi; Emily R Perito; John F Pohl; Sue Rhee; Sarah J Schwarzenberg; Uzma Shah; David Troendle; Steven L Werlin; Michael Wilschanski; M Bridget Zimmerman; Mark E Lowe; Aliye Uc Journal: J Pediatr Gastroenterol Nutr Date: 2019-08 Impact factor: 2.839
Authors: Chinenye R Dike; Bridget Zimmerman; Yuhua Zheng; Michael Wilschanski; Steven L Werlin; David Troendle; Uzma Shah; Sarah Jane Schwarzenberg; John Pohl; Emily R Perito; Chee Y Ooi; Jaimie D Nathan; Veronique D Morinville; Brian McFerron; Maria Mascarenhas; Asim Maqbool; Quin Liu; Tom K Lin; Sohail Z Husain; Melvin B Heyman; Tanja Gonska; Matthew J Giefer; Cheryl E Gariepy; Douglas S Fishman; Melena Bellin; Bradley Barth; Maisam Abu-El-Haija; Mark E Lowe; Aliye Uc Journal: J Pediatr Gastroenterol Nutr Date: 2020-07 Impact factor: 3.288
Authors: Julia Mayerle; Matthias Sendler; Eszter Hegyi; Georg Beyer; Markus M Lerch; Miklós Sahin-Tóth Journal: Gastroenterology Date: 2019-01-18 Impact factor: 22.682