André Strohmeyer

Publications of André Strohmeyer

• MALDI-TOF mass spectrometry screening of cholelithiasis risk markers in the gene of HNF1alpha.

  Authors: Dominique Richter, Simone Harsch, André Strohmeyer, Satoko Hirobe-Jahn, Silke Schimmel, Olga Renner, Oliver Müller, Elke Schäffeler, Wolfgang Kratzer, Matthias Schwab, Eduard F Stange

  Journal of proteomics. 05/2012;

  In recent years MALDI-TOF MS gained in importance for high-throughput DNA analysis. In the present study this technique was used for the pathogenetic analysis of gallstone disease. The intestinalIn recent years MALDI-TOF MS gained in importance for high-throughput DNA analysis. In the present study this technique was used for the pathogenetic analysis of gallstone disease. The intestinal apical sodium-dependent bile acid transporter (ASBT) shows a genetic association with gallstone disease. ASBT has 3 binding sites in its 5'UTR for hepatocyte nuclear factor 1alpha (HNF1alpha). We hypothesized that genetic alterations in the HNF1alpha gene could influence ASBT expression. The gene HNF1alpha was sequenced in 46 Stuttgart random samples, composed of 16 controls and 30 gallstone patients. Subsequently, two independent cohorts (Stuttgart: 67 gallstones carriers, 109 controls, Leutkirch: 112 gallstone carriers, 99 controls) were screened by MALDI-TOF MS. The subjects were further divided to gender and weight. 24 known polymorphisms and two novel SNPs in the 3'UTR of HNF1alpha were detected (c.*220G>A and c.*1151G>A). After gender-specific sub-division of the pooled cohorts, 4 SNPs result in significant differences between male gallstone carriers and male controls (Stuttgart/Leutkirch: rs2255531 OR=2.78; p=0.006, rs1169288 OR=2.13; p=0.032 rs7310409 OR=2.34; p=0.025 and rs1169294 OR=2.13; p=0.031). Two novel variants in the 3'UTR of HNF1alpha were detected and four SNPs of HNF1alpha show a significant association to cholelithiasis in male gallstone patients. This article is part of a Special Issue entitled: Genome regulation.

• Diminished Expression of Apical Sodium-Dependent Bile Acid Transporter in Gallstone Disease Is Independent of Ileal Inflammation.

  Authors: Arthur Holzer, Simone Harsch, Olga Renner, André Strohmeyer, Silke Schimmel, Jan Wehkamp, Peter Fritz, Eduard F Stange

  Digestion. 11/2008; 78(1):52-59.

  Background: Non-obese gallstone patients exhibit a diminished expression of apical sodium-dependent bile acid transporter (ASBT) in terminal ileum. Crohn's ileitis demonstrates a significantBackground: Non-obese gallstone patients exhibit a diminished expression of apical sodium-dependent bile acid transporter (ASBT) in terminal ileum. Crohn's ileitis demonstrates a significant downregulation of this transporter. Aim: To test whether subclinical ileal inflammation contributes to gallstone disease. Methods: Biopsies from terminal ileum of female subjects with gallstone disease (n = 7), active Crohn's disease (n = 17) and controls (n = 22) were investigated. mRNA expression of ASBT, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-8, c-jun and c-fos was measured. c-jun and c-fos protein levels were determined and hematoxylin and eosin staining was applied for ileal histology. Results: ASBT expression was comparably low both in gallstone (47% of controls, p = 0.0093) and Crohn's disease (42% of controls, p = 0.0008). In gallstone disease there was a non-significant trend towards elevated TNF-alpha and IL-1beta, but all cytokines were increased in active Crohn's disease. c-jun and c-fos were slightly diminished in patients with gallstones. Neither cytokines nor transcription factors correlated significantly with ASBT. The gallstone-associated ileal biopsies exhibited no histological inflammation. Conclusion: Although the expression of ASBT was similarly diminished in both gallstone and Crohn's disease, subclinical ileal inflammation does not appear to be relevant in gallstone patients. The mechanisms of transcriptional repression of ASBT in both diseases are apparently different.

• Reduced ileal expression of organic solute transporter alpha and beta (OSTalpha -OSTbeta ) in non-obese gallstone disease.

  Authors: Olga Renner, Simone Harsch, André Strohmeyer, Silke Schimmel, Eduard F Stange

  Journal of lipid research. 06/2008;

  Cholelithiasis is a multifactorial process and several mechanisms have been postulated. A decreased expression of the ileal apical sodium-dependent bile acid transporter (ASBT) and of the cytosolicCholelithiasis is a multifactorial process and several mechanisms have been postulated. A decreased expression of the ileal apical sodium-dependent bile acid transporter (ASBT) and of the cytosolic ileal lipid binding protein (ILBP) was recently described in female non-obese patients. The role of the recently identified organic solute transporter (OSTa-OSTss) in gallstone pathogenesis remains still unclear. Therefore we performed analysis of OSTa-OSTss in gallstone patients, regarding body weight. Ileal mucosal biopsies were collected during routinely colonoscopy from female gallstone carriers (n=19) and controls (n=34). OSTa-OSTss mRNA expression was measured using the LightCycler sequence detection system; protein was analyzed by immunohistochemistry and Western blot. The mRNA expression of OSTa-OSTss was significantly (OSTa: 3.3-fold, p=0.006; OSTss: 2.6-fold, p=0.03) reduced in normal weight but not overweight gallstone carriers compared to controls. OSTa-OSTss protein levels also showed a reduction by 40-67%. The expression of OSTa-OSTss correlated positively with ASBT (r=0.65; 0.58, respectively), ILBP (r=0.77; 0.67), the farnesoid X receptor (FXR) (r=0.58; 0.50). Fibroblast growth factor-19 (FGF-19) showed a 2.8-fold (p=0.06) and liver receptor homolog-1 (LRH-1) a 2.0-fold reduction (p=0.04) in non-obese patients. In conclusion, an impaired function of all three ileal bile acid transporters may lead to low ileal bile acid reabsorption, an altered bile acid pool composition and therefore contribute to the formation of gallstones in non-obese.