title: Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway analysis in inflammatory bowel disease.
abstract: BACKGROUND
  The Th17/IL23 pathway has both genetically and biologically been implicated in the pathogenesis of the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. So far, it is unknown whether and how associated risk variants affect expression of the genes encoding for Th17/IL23 pathway proteins.
  
  
  METHODS
  Ten IBD-associated SNPs residing near Th17/IL23 genes were used to construct a genetic risk model in 753 Dutch IBD cases and 1045 controls. In an independent cohort of 40 Crohn's disease, 40 ulcerative colitis, and 40 controls, the genetic risk load and presence of IBD were correlated to quantitative PCR-generated messenger RNA (mRNA) expression of 9 representative Th17/IL23 genes in both unstimulated and PMA/CaLo stimulated peripheral blood mononuclear cells. In 1240 individuals with various immunological diseases with whole genome genotype and mRNA-expression data, we also assessed correlation between genetic risk load and differential mRNA expression and sought for SNPs affecting expression of all currently known Th17/IL23 pathway genes (cis-expression quantitative trait locus).
  
  
  RESULTS
  The presence of IBD, but not the genetic risk load, was correlated to differential mRNA expression for IL6 in unstimulated peripheral blood mononuclear cells and to IL23A and RORC in response to stimulation. The cis-expression quantitative trait locus analysis showed little evidence for correlation between genetic risk load and mRNA expression of Th17/IL23 genes, because we identified for only 2 of 22 Th17/IL23 genes a cis-expression quantitative trait locus single nucleotide polymorphism that is also associated to IBD (STAT3 and CCR6).
  
  
  CONCLUSIONS
  Our results suggest that only the presence of IBD and not the genetic risk load alters mRNA expression levels of IBD-associated Th17/IL23 genes.
authors.affiliation: Departments of *Genetics, and †Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Fransen
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Sommeren
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Westra
authors.forename: Monique
authors.initials: M
authors.lastname: Veenstra
authors.forename: Letitia E
authors.initials: LE
authors.lastname: Lamberts
authors.forename: Rutger
authors.initials: R
authors.lastname: Modderman
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fu
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
authors.forename: Cleo C
authors.initials: CC
authors.lastname: van Diemen
mesh_terms: D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger