Format

Send to

Choose Destination
Clin Transl Gastroenterol. 2018 Nov 12;9(11):204. doi: 10.1038/s41424-018-0069-5.

SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

Author information

1
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
2
Shanghai Institute of Pancreatic Diseases, Shanghai, China.
3
Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Institute of Medical Genetics, Tongji University, Shanghai, China.
4
Medical Service Research Division, the Naval Medical Research Institute, Second Military Medical University, Shanghai, China.
5
Center for Translational Medicine, Second Military Medical University, Shanghai, China.
6
Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, China.
7
Key Laboratory of Developmental Genetics and Neuropsychiatric Diseases (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
8
UMR1078 ″Génétique, Génomique Fonctionnelle et Biotechnologies″, INSERM, EFS - Bretagne, Université de Brest, CHRU Brest, Brest, France.
9
Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK.
10
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China. zhaoshenli@hotmail.com.
11
Shanghai Institute of Pancreatic Diseases, Shanghai, China. zhaoshenli@hotmail.com.
12
UMR1078 ″Génétique, Génomique Fonctionnelle et Biotechnologies″, INSERM, EFS - Bretagne, Université de Brest, CHRU Brest, Brest, France. Jian-Min.Chen@univ-brest.fr.
13
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China. liaozhuan@smmu.edu.cn.
14
Shanghai Institute of Pancreatic Diseases, Shanghai, China. liaozhuan@smmu.edu.cn.

Abstract

OBJECTIVES:

Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.

METHODS:

We performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene-environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan-Meier model.

RESULTS:

We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups.

CONCLUSIONS:

We provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene-environment interactions were also identified.

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center