Chymotrypsinogen C Genetic Variants, Including c.180TT, Are Strongly Associated With Chronic Pancreatitis in Pediatric Patients.

Autor: Grabarczyk AM; Department of Medical Genetics, Institute of Mother and Child†Department of Gastroenterology, Hepatology and Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw‡Department of Surgery and Surgical Nursing, Jan Kochanowski University of Kielce§Department of Molecular Diagnostics, Oncology Center of the Holy Cross, Kielce, Poland., Oracz G, Wertheim-Tysarowska K, Kujko AA, Wejnarska K, Kolodziejczyk E, Bal J, Koziel D, Kowalik A, Gluszek S, Rygiel AM
Jazyk: angličtina
Zdroj: Journal of pediatric gastroenterology and nutrition [J Pediatr Gastroenterol Nutr] 2017 Dec; Vol. 65 (6), pp. 652-657.
DOI: 10.1097/MPG.0000000000001767
Abstrakt: 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.
Databáze: MEDLINE
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