SPINK1 Promoter Variants in Chronic Pancreatitis

Pancreas
Eszter HegyiHungarian Pancreatic Study Group

Abstract

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). One hundred CP patients (cases) and 100 controls with no pancreatic disease from the Hungarian National Pancreas Registry were enrolled. Direct sequencing of SPINK1 promoter region was performed. Functional characterization of variants was carried out using luciferase reporter gene assay. Two common polymorphisms (c.-253T>C and c.-807C>T) were found in both cases and controls. Variant c.253T>C was enriched in cases relative to controls (odds ratio, 2.1; 95% confidence interval, 1.2-3.8; P = 0.015). Variant c.-215G>A was detected in 3 of 100 cases; always linked with the pathogenic variant c.194+2T>C. Novel promoter variants c.-14G>A, c.-108G>T, and c.-246A>G were identified in 1 case each. Functional analysis showed decreased promoter activity for variants c.-14G>A (80%), c.-108G>T (31%), and c.-246A>G (47%) whereas activity of variant c.-215G>A was increased (201%) and variant c.-253T>C was unchanged compared with wild type. The common promoter variant c.-253T>C was associated wit...Continue Reading

References

Dec 16, 1987·Biochemical and Biophysical Research Communications·A HoriiK Matsubara
Sep 3, 1998·The New England Journal of Medicine·N SharerJ Braganza
Jul 26, 2002·Journal of Inherited Metabolic Disease·D N Cooper
Nov 28, 2002·Digestive Diseases and Sciences·Ezio GaiaArduino Carlo
Mar 22, 2003·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Niels TeichVolker Keim
Dec 23, 2003·Cancer Biology & Therapy·Hiroyuki MatsubayashiMichael Goggins
Jun 28, 2005·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Kiyoshi KumeTooru Shimosegawa
Jul 11, 2006·European Journal of Human Genetics : EJHG·Emmanuelle MassonClaude Férec
Sep 9, 2006·Journal of Gastroenterology and Hepatology·Tooru ShimosegawaAtsushi Masamune
Mar 3, 2007·Immunogenetics·Martin C WapenaarCisca Wijmenga
Apr 21, 2007·Pancreas·Atsushi MasamuneTooru Shimosegawa
Jun 15, 2007·European Journal of Human Genetics : EJHG·Arnaud BoullingClaude Férec
Jan 14, 2009·World Journal of Gastroenterology : WJG·Swapna MahurkarGiriraj Ratan Chandak
May 26, 2011·European Journal of Human Genetics : EJHG·Arnaud BoullingClaude Férec
Feb 22, 2012·Pancreas·Arnaud BoullingClaude Férec
Apr 25, 2012·Journal of Gastroenterology·Kiyoshi KumeTooru Shimosegawa
Apr 28, 2012·The Journal of Biological Chemistry·András Szabó, Miklós Sahin-Tóth
Aug 21, 2013·Nature Genetics·Heiko WittMiklós Sahin-Tóth

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Citations

Jul 1, 2016·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Robert A MoranVikesh K Singh
Jul 20, 2016·Human Mutation·Arnaud BoullingClaude Férec
May 26, 2017·Digestive Diseases and Sciences·Eszter Hegyi, Miklós Sahin-Tóth

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