title: Association of a Nkx2-3 polymorphism with Crohn's disease and expression of Nkx2-3 is up-regulated in B cell lines and intestinal tissues with Crohn's disease.
abstract: OBJECTIVE
  To replicate the association of Nkx2-3 rs10883365 SNP with Crohn's disease in patients from a familial IBD registry from the central Pennsylvania area and study mRNA and protein expression of Nkx2-3 in CD patients.
  
  
  METHODS
  We genotyped the Nkx2-3 rs10883365 SNP in 75 CD patients,137 non-CD family members and 118 unrelated healthy controls from EBV-transformed B cell lines of a familial IBD registry in central Pennsylvania. mRNA and protein expression levels of Nkx2-3 were measured by RT-PCR and Western blot, respectively.
  
  
  RESULTS
  rs10883365 was found to be associated with CD. A significant difference between the homozygous variant genotype (GG) compared to the wild type sequence (AA) was observed between CD and individuals without IBD, including both non-IBD family members from the familial IBD registry and unrelated healthy controls. However, there was not a significant difference between CD and non-IBD related family members. mRNA and protein expression levels of Nkx2-3 were increased in CD compared with non-CD sibling and healthy controls. A total of 16 sibling pairs were examined, and the mRNA and protein expression levels of Nkx2-3 from 12 of the sibling pairs (75%) were increased in the CD individual compared with the non-CD sibling. mRNA expression levels of Nkx2-3 were increased in diseased tissues compared with adjacent normal tissues in 7 of 9 patients (77.8%).
  
  
  CONCLUSIONS
  Nkx2-3 is genetically associated with CD and is up-regulated in CD, suggesting that Nkx2-3 is involved in the pathogenesis of CD.
authors.affiliation: Department of Surgery, the Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Lin
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Kelly
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Poritz
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Tongyi
authors.initials: T
authors.lastname: Li
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Walter A
authors.initials: WA
authors.lastname: Koltun