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World J Gastroenterol. Jan 14, 2011; 17(2): 197-206
Published online Jan 14, 2011. doi: 10.3748/wjg.v17.i2.197
Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease
Vibeke Andersen, Jane Christensen, Anja Ernst, Bent A Jacobsen, Anne Tjønneland, Henrik B Krarup, Ulla Vogel
Vibeke Andersen, Department of Medical, Viborg Regional Hospital, 8800 Viborg, Denmark
Jane Christensen, Anne Tjønneland, Institute of Cancer Epidemiology, Danish Cancer Society, 2100 Copenhagen, Denmark
Anja Ernst, Henrik B Krarup, Department of Clinical Biochemistry, Aarhus University Hospital, 9000 Aalborg, Denmark
Bent A Jacobsen, Department of Medical Gastroenterology, Aarhus University Hospital, 9000 Aalborg, Denmark
Ulla Vogel, National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark
Ulla Vogel, Institute for Science, Systems and Models, University of Roskilde, 4000 Roskilde, Denmark
Ulla Vogel, National Research Centre for the Working Environment, 2100 Copenhagen, Denmark
Author contributions: Andersen V and Vogel U designed and performed the research and wrote the paper; Andersen V, Ernst A, Jacobsen BA and Krarup HB conceived and designed the patient cohort; Christensen J and Tjønneland A performed the data analyses; all authors approved the manuscript.
Supported by This project was supported by the “Familien Erichsen Mindefond”, the Lundbeck Foundation, the Danish Research Council, the Western Danish Research Forum for Health Science, the County of Viborg, the Danish Colitis-Crohn Association, “John M Klein og hustrus mindelegat”, and the A.P. Møller Foundation for the Advancement of Medical Science
Correspondence to: Vibeke Andersen, PhD, Department of Medical, Viborg Regional Hospital, 8800 Viborg, Denmark. va9791@gmail.com
Telephone: +45-89272641 Fax: +45-89273484
Received: May 28, 2010
Revised: August 14, 2010
Accepted: August 21, 2010
Published online: January 14, 2011
AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD).
METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn’s disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models.
RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively).
CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.
