title: In gastroesophageal reflux disease, differential gene expression in the duodenum points towards enhanced chylomicron production and secretion.
abstract: BACKGROUND
  Duodenal signaling affects esophageal motility and perception, both pathophysiological factors in gastroesophageal reflux disease (GERD). Duodenal gene expression abnormalities, contributing to altered esophageal sensorimotor function, have not been reported to date.
  
  
  OBJECTIVE
  To identify differentially expressed genes in GERD patients' duodenum.
  
  
  METHODS
  Twenty GERD patients (total 24-h acid exposure 6-12%, SAP ≥95%) and ten healthy controls (HC) were included. Two weeks prior to duodenal biopsy collection, ten patients discontinued proton pump inhibitor (PPI) treatment and ten took maximum dose PPI. RNA was profiled on an Affymetrix Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA). Genes exhibiting a fold change ≥ 1.4 (t test p value <1E-4) were considered differentially expressed. A subset of 21 differentially expressed genes was selected for confirmatory TaqMan low-density array RT-PCR. Mucosal apolipoprotein A-IV (apoA-IV) and cholecystokinin (CCK) concentrations were determined by ELISA and RIA, respectively.
  
  
  RESULTS
  In GERD patients off PPI, 23 up- and 23 down-regulated genes relative to HC were found. In GERD patients on PPI, 33 and five genes were higher, respectively, lower expressed. The majority of up-regulated genes were associated with lipid absorption, particularly triglyceride resynthesis and intracellular vesicular transport, rate-limiting processes for chylomicron production and secretion. Differential expression of 11 genes was confirmed by RT-PCR. Mucosal apoA-IV and CCK concentrations (signaling proteins released upon chylomicron secretion) were similar in GERD patients and HC.
  
  
  CONCLUSIONS
  The identified mRNA expression differences suggest that in GERD patients' duodenum, the chylomicron production and secretion potential is elevated, and may underlie a mechanism by which postprandial duodenal signaling contributes to GERD symptom generation.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Durk R
authors.initials: DR
authors.lastname: de Vries
authors.forename: José J M
authors.initials: JJ
authors.lastname: ter Linde
authors.forename: Ofke S
authors.initials: OS
authors.lastname: van Boxel
authors.forename: Margot A
authors.initials: MA
authors.lastname: van Herwaarden
authors.forename: Pierre
authors.initials: P
authors.lastname: Shephard
authors.forename: Michael M
authors.initials: MM
authors.lastname: Geng
authors.forename: Matthijs P
authors.initials: MP
authors.lastname: Schwartz
authors.forename: Melvin
authors.initials: M
authors.lastname: Samsom
mesh_terms: D000328:Adult; D001054:Apolipoproteins A / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002914:Chylomicrons / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation; D004386:Duodenum / Q000378:metabolism; D050782:Esophageal pH Monitoring; D004945:Esophagoscopy / Q000379:methods; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D001054:Apolipoproteins A; D002914:Chylomicrons; D054328:Proton Pump Inhibitors; C022205:apolipoprotein A-IV