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

Abstract

In recent years MALDI-TOF MS gained 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 by 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 resulted 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 Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.

• 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: Journal of proteomics (J Proteomics) Vol. 75 Issue 12 Pg. 3386-99 (Jun 27 2012) ISSN: 1876-7737 [Electronic] Netherlands
• PMID: 22569176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Genetic Markers
• Hepatocyte Nuclear Factor 1-alpha
• DNA

Topics

• Adult
• Aged
• Biomarkers (analysis)
• Cholelithiasis (genetics)
• DNA (analysis, genetics)
• Genetic Markers (genetics)
• Genetic Predisposition to Disease (genetics)
• Genetic Testing (methods)
• Hepatocyte Nuclear Factor 1-alpha (genetics)
• Humans
• Male
• Middle Aged
• Sequence Analysis, DNA (methods)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)