title: 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.affiliation: Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology and University of Tübingen, Stuttgart, Germany. Dominique.Richter@ikp-stuttgart.de
authors.forename: Dominique
authors.initials: D
authors.lastname: Richter
authors.forename: Simone
authors.initials: S
authors.lastname: Harsch
authors.forename: André
authors.initials: A
authors.lastname: Strohmeyer
authors.forename: Satoko
authors.initials: S
authors.lastname: Hirobe-Jahn
authors.forename: Silke
authors.initials: S
authors.lastname: Schimmel
authors.forename: Olga
authors.initials: O
authors.lastname: Renner
authors.forename: Oliver
authors.initials: O
authors.lastname: Müller
authors.forename: Elke
authors.initials: E
authors.lastname: Schäffeler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kratzer
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.forename: Eduard F
authors.initials: EF
authors.lastname: Stange
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002769:Cholelithiasis / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D051538:Hepatocyte Nuclear Factor 1-alpha; D004247:DNA