Genetic variants of lipase activity in chronic pancreatitis: Table 1

Kirsten, Holger; Scholz, Markus; Kovacs, Peter; Grallert, Harald; Peters, Annette; Strauch, Konstantin; Frank, Josef; Rietschel, Marcella; Nöthen, Markus M.; Witt, Heiko; Rosendahl, Jonas

doi:10.1136/gutjnl-2015-309521

Cited by 8 publications

(5 citation statements)

References 3 publications

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“…61 Interestingly, the CEL protein carries blood group antigens and a GWAS in 2015 indicated that fucosyl-transferase 2 nonsecretor status and blood group B are risk factors for CP. 62 Although other studies in ethnically mixed cohorts failed to replicate this association, 63,64 with the exception of azathioprine-induced pancreatitis in patients with inflammatory bowel disease, 65 it is still interesting to speculate that the observed effects might have been due to changes in CEL folding or trafficking.…”

Section: Mis-folding-associated Cel Mutations and Cel-hyb Allelementioning

confidence: 99%

Genetics, Cell Biology, and Pathophysiology of Pancreatitis

et al. 2019

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Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of mutations in genes involved in the digestive protease-antiprotease pathway has lent additional support to the notion that pancreatitis is a disease of autodigestion. Clinical and experimental observations have provided compelling evidence that premature intrapancreatic activation of digestive proteases is critical in pancreatitis onset. However, disease course and severity are mostly governed by inflammatory cells that drive local and systemic immune responses. In this article, we review the genetics, cell biology, and immunology of pancreatitis with a focus on protease activation pathways and other early events.

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Section: Mis-folding-associated Cel Mutations and Cel-hyb Allelementioning

confidence: 99%

Genetics, Cell Biology, and Pathophysiology of Pancreatitis

et al. 2019

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“…Also for chronic pancreatitis, a study has reported that ABO blood group status, in particular the B phenotype, is a risk factor for this inflammatory condition (60,61). However, others have found no association between ABO blood groups and chronic pancreatitis (62,63). Moreover, FUT2-negative status has been linked to chronic pancreatitis (60, 61) but not to pancreatic cancer (31,32), and it is an open question whether the inactivation of the FUT2 gene product represents a detrimental or beneficial effect with regard to human health.…”

Section: Carboxyl-ester Lipase Contains Abo Blood Group Determinantsmentioning

confidence: 99%

The mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinants

Jellas

Johansson

Fjeld

et al. 2018

Journal of Biological Chemistry

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Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C terminus of CEL/FAPP. We here assessed the expression of human CEL in malignant pancreatic lesions and cell lines. CEL was not detectably expressed in neoplastic cells, implying that FAPP is unlikely to be a glycoisoform of CEL in pancreatic cancer. Testing of the mAb16D10 antibody in glycan microarrays then demonstrated that it recognized structures containing terminal GalNAc-␣1,3(Fuc-␣1,2)Gal (blood group A antigen) and also repeated protein sequences containing GalNAc residues linked to Ser/Thr (Tn antigen), findings that were supported by immunostainings of human pancreatic tissue. To examine whether the CEL glycoprotein might be modified by blood group antigens, we used high-sensitivity MALDI-TOF MS to characterize the released O-glycan pool of CEL immunoprecipitated from human pancreatic juice. We found that the O-glycome of CEL consisted mainly of core 1/core 2 structures with a composition depending on the subject's FUT2 and ABO gene polymorphisms. Thus, among digestive enzymes secreted by the pancreas, CEL is a glycoprotein with some unique characteristics, supporting the view that it could serve additional biological functions to its cholesteryl esterase activity in the duodenum.

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“…Blood group antigens attached to the surface of the CEL protein and fucosyltransferase 2 (FUT2) non-secretor status (which affects the status of the ABO antigens, especially blood group B) was associated in a genomewide association study (GWAS) [37]. However, in following studies, this association could not be confirmed apart from an association between blood group B and azathioprine-induced AP [38][39][40].…”

Section: Carboxyl Ester Lipase (Cel-hypb1 Allele)mentioning

confidence: 98%

Genetic Testing in Acute and Chronic Pancreatitis

Piseddu

Vielhauer

Mayerle

2022

Curr Treat Options Gastro

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Purpose of review Premature intracellular activation of pancreatic zymogens leads to the initiation of pancreatitis, which in up to 25% leads to chronic tissue destruction, exocrine and endocrine organ failure, and a moderate increased risk of pancreatic cancer development. Whereas in many cases, the trigger of organ damage is identified, diagnostic workup in a significant number of patients does not reveal the underlying etiology of pancreatic inflammation. In these cases, alterations in different pancreatic susceptibility genes have been described to be directly or indirectly involved in disease development. In this review, we want to give an update on the most important pancreatitis risk genes and their impact on clinical diagnostics and risk stratification as well as possible treatment options. Recent findings Genetic testing is not routinely implemented in the diagnostic workup of acute or chronic pancreatitis, as most genetic variations are not considered causative for pancreatitis development but confer increased susceptibility and genetic testing rarely changes disease management. However, in patients with recurrent pancreatitis episodes of unknown etiology after intensive diagnostic work-up, in patients with a family history of pancreatitis, relatives of patients with hereditary pancreatitis, and patients with disease onset at young age, genetic testing and counseling is recommended. Besides well-established susceptibility genes such as PRSS1, SPINK1, CPA1, and CFTR, additional genes such as TRPV6 and rare genetic alterations in established risk genes have been recently identified which significantly contribute to the risk of pancreatitis, involving different molecular mechanisms. Summary When genetic testing is considered, we propose screening at least for PRSS1, SPINK1, CPA1, and CFTR gene variants. The emergence of next-generation sequencing methods could also render larger gene panels possible and clinically meaningful to detect rare variants with high-risk phenotypes. Here we summarize, evaluate, and convey in the form of practical recommendations the current level of knowledge with respect to definition, etiology, and genetic diagnostics of all forms of inherited pancreatitis.

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Genetic variants of lipase activity in chronic pancreatitis: Table 1

Cited by 8 publications

References 3 publications

Genetics, Cell Biology, and Pathophysiology of Pancreatitis

Genetics, Cell Biology, and Pathophysiology of Pancreatitis

The mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinants

Genetic Testing in Acute and Chronic Pancreatitis

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