SPINK1 Promoter Variants in Chronic Pancreatitis.

Objectives: Serine protease inhibitor Kazal type 1 (SPINK1) provides an important line of defense against premature trypsinogen activation within the pancreas. Our aim was to identify pathogenic SPINK1 promoter variants associated with chronic pancreatitis (CP).

Methods: One hundred CP patients (cases) and 100 controls with no pancreatic disease from the Hungarian National Pancreas Registry were enrolled.

Functional significance of SPINK1 promoter variants in chronic pancreatitis.

Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers.

Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study.

Objective: Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort.

Untreated celiac disease in a patient with dermatitis herpetiformis leading to a small bowel carcinoma.

Usually, celiac disease has a benign course, though the overall morbidity and mortality have increased. Treatment with a gluten-free diet restores the damaged intestinal mucosa. In rare cases a small bowel adenocarcinoma develops.

[Hepatitis B; sometimes co-infection with hepatitis D].

Background: The Hepatitis delta virus (HDV) is a defect RNA virus that requires the presence of the hepatitis B virus (HBV) for cellular infection. Worldwide, 350 million people are infected with HBV; 5% of these are superinfected with HDV. A chronic superinfection with HDV has a higher morbidity and mortality rate.

Genetic factors in chronic pancreatitis; implications for diagnosis, management and prognosis.

Chronic pancreatitis (CP) is a clinical situation with persisting inflammation leading to destruction of the pancreas ensuing endocrine and exocrine failure. There are 4 subtypes: hereditary, idiopathic, alcoholic and tropical pancreatitis. Genetic factors can explain a significant proportion of CP cases.

[Dutch patients with hereditary pancreatitis; high mutation frequency, relatively little pain].

Objective: To assess genetic, clinical and morphological characteristics of hereditary pancreatitis, a rare type of chronic pancreatitis with an early onset of symptoms, which is, among others, caused by mutations in the PRSS1 gene.

Design: Observational cohort study.

Method: The study population consisted of 496 patients (27,375 person-years) who were referred to Radboud University Nijmegen Medical Centre for molecular diagnosis of hereditary pancreatitis during period 2000 to 2007.

Tropical calcific pancreatitis and its association with CTRC and SPINK1 (p.N34S) variants.

Background: Tropical calcific pancreatitis (TCP) is a relatively common form of chronic pancreatitis in parts of Asia and Africa. The SPINK1 variant p.N34S is strongly associated with TCP, but other genetic factors remain to be defined.