TY - JOUR
T1 - 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
AU - Yu, Wei
AU - Lin, Zhenwu
AU - Kelly, Ashley A.
AU - Hegarty, John P.
AU - Poritz, Lisa
AU - Wang, Yunhua
AU - Li, Tongyi
AU - Schreiber, Stefan
AU - Koltun, Walter
N1 - Funding Information:
Authors thank Drs. A. Franke and A. Ruether for their help in the genotype analysis with SNPlex™ Genotype system, and thank Kathryn A. Byrnes and Anthony W. Gebhard for their help in samples preparation. This work was supported by a grant from the Philadelphia Health Care trust, the Carlino fund for IBD research at the Milton S. Hershey Medical center, Penn State College of Medicine, and the Milton S. Hershey Penn State College of Medicine Surgery Research Feasibility Grant.
PY - 2009/9
Y1 - 2009/9
N2 - Aim: 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. Materials and 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.
AB - Aim: 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. Materials and 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.
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U2 - 10.1016/j.crohns.2009.04.003
DO - 10.1016/j.crohns.2009.04.003
M3 - Article
C2 - 21172269
AN - SCOPUS:67651085303
SN - 1873-9946
VL - 3
SP - 189
EP - 195
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 3
ER -