Association Analysis of Genetic Variants in the Myosin IXB Gene in Acute Pancreatitis

Nijmeijer, Rian M.; Santvoort, Hjalmar C. van; Zhernakova, Alexandra; Teller, Steffen; Scheiber, Jonas A.; Kovel, Carolien G.F. de; Besselink, Marc G.; Visser, J.H.M.; Lutgendorff, Femke; Bollen, Thomas L.; Boermeester, Marja A.; Rijkers, Ger T.; Weiss, Frank Ulrich; Mayerle, Julia; Lerch, Markus M.; Gooszen, Hein G.; Akkermans, L.M.A.; Wijmenga, Cisca

doi:10.1371/journal.pone.0085870

Cited by 14 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the genetic association study, a previously described cohort of 387 patients with a first episode of AP was used [26] . All patients or their legal representatives gave their written informed consent, and the ethics review boards of all participating hospitals approved the study protocol.…”

Section: Methodsmentioning

confidence: 99%

Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundInfectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the pancreas, exhibits anti-inflammatory effects by inhibiting NF-κB activation and is implicated in maintaining intestinal barrier integrity and preventing bacterial overgrowth and translocation. Here we explore, with the aid of complementary animal and human experiments, the potential role of FXR in acute pancreatitis.MethodsExperimental acute pancreatitis was induced using the CCK-analogue cerulein in wild-type and Fxr-/- mice. Severity of acute pancreatitis was assessed using histology and a semi-quantitative scoring system. Ileal permeability was analyzed in vitro by Ussing chambers and an in vivo permeability assay. Gene expression of Fxr and Fxr target genes was studied by quantitative RT-PCR. Serum FGF19 levels were determined by ELISA in acute pancreatitis patients and healthy volunteers. A genetic association study in 387 acute pancreatitis patients and 853 controls was performed using 9 tagging single nucleotide polymorphisms (SNPs) covering the complete FXR gene and two additional functional SNPs.ResultsIn wild-type mice with acute pancreatitis, ileal transepithelial resistance was reduced and ileal mRNA expression of Fxr target genes Fgf15, SHP, and IBABP was decreased. Nevertheless, Fxr-/- mice did not exhibit a more severe acute pancreatitis than wild-type mice. In patients with acute pancreatitis, FGF19 levels were lower than in controls. However, there were no associations of FXR SNPs or haplotypes with susceptibility to acute pancreatitis, or its course, outcome or etiology.ConclusionWe found no evidence for a major role of FXR in acute human or murine pancreatitis. The observed altered Fxr activity during the course of disease may be a secondary phenomenon.

show abstract

Section: Methodsmentioning

confidence: 99%

Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Preliminary reports which await further validation include CTSB [60], MYO9B [61], and UBR1 [62], or the association of an increased pancreatitis risk with ABO blood group and the so-called “secretor status,” which is determined by a mutation of the fucosyltransferase gene FUT2 [29, 63]. Additional genetic variants are being evaluated and will likely be added to this list in the future.…”

Section: Recurrent Acute and Chronic Pancreatitis: Distinction And Etmentioning

confidence: 99%

Etiology and Risk Factors of Acute and Chronic Pancreatitis

Weiss

Laemmerhirt

Lerch³

2019

Visc Med

View full text Add to dashboard Cite

Based on the recognition of common etiological and genetic risk factors, acute and chronic pancreatitis are increasingly regarded as a continuum of the same disease, with a significant overlap of clinical manifestations and phenotypes but distinct morphological and imaging appearances. Recent population-based and cohort studies have found that tobacco smoke conveys a greater risk than immoderate alcohol consumption for the development of chronic pancreatitis, and hypertriglyceridemia has been identified as a risk factor for acute pancreatitis – even when plasma levels are only mildly elevated. Hereditary pancreatitis, in its autosomal dominant form, is associated with mutations in the cationic trypsinogen gene (PRSS1), whereas a number of germline variations in other genes have been found to represent risk factors for chronic as well as acute pancreatitis. For now, most of these involve the pancreatic digestive protease/antiprotease system. Oftentimes, affected patients are burdened with multiple or accumulating risk factors, and genetic traits when combined with environmental toxins compound the chance of developing the disease. Determining the underlying etiology of pancreatitis is worth the effort since formerly intractable varieties such as autoimmune pancreatitis are now becoming increasingly treatable, and subtype-specific therapeutic modalities may become available.

show abstract

“…Furthermore, changes in pancreatic epithelial tight-junctions are one of the earliest events that occur in AP in murine models. The MYO9B gene encodes for an unconventional myosin compound that can activate the domain of the GTPase protein (Rho-GAP), which regulates the tight-junction assembly and maintains the selectivity of the paracellular pathway in enterocytes ( 17 , 21 , 22 ). Genetic abnormalities in the MY09B gene have been found in both IBD and celiac disease, two entities where impairment of intestinal patency plays an important role.…”

Section: Acute Pancreatitismentioning

confidence: 99%

Pancreatic Involvement in Pediatric Inflammatory Bowel Disease

et al. 2017

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic condition that includes two clinical entities: Crohn’s disease and ulcerative colitis. Although both entities mainly affect the gastrointestinal tract are considered multisystemic diseases and may present extraintestinal manifestations involving other organs and systems. Pancreatic involvement in Pediatric IBD includes a heterogeneous group of clinical entities like acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, asymptomatic exocrine pancreatic insufficiency, increased pancreatic enzyme levels, structural abnormalities, and granulomatous inflammation. Although the mechanism for pancreatic involvement in IBD is not clearly elucidated, is important to keep in mind the association of these two entities in order to perform a prompt diagnosis and establish an appropriate treatment. The objective of this review is to update the available evidence on pancreatic involvement in children with IBD.

show abstract

Association Analysis of Genetic Variants in the Myosin IXB Gene in Acute Pancreatitis

Cited by 14 publications

References 44 publications

Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

Etiology and Risk Factors of Acute and Chronic Pancreatitis

Pancreatic Involvement in Pediatric Inflammatory Bowel Disease

Contact Info

Product

Resources

About