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Polymorphisms in NF-?B, PXR, LXR, PPAR? and risk of inflammatory bowel disease.


ABSTRACT: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD).Genotypes of nuclear factor (NF)-?B (NFKB1) NF?B -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-? (PPAR?) PPAR? 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.The PXR A7635G variant, the PPAR? 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).Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.

SUBMITTER: Andersen V 

PROVIDER: S-EPMC3020373 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease.

Andersen Vibeke V   Christensen Jane J   Ernst Anja A   Jacobsen Bent A BA   Tjønneland Anne A   Krarup Henrik B HB   Vogel Ulla U  

World journal of gastroenterology 20110101 2


<h4>Aim</h4>To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD).<h4>Methods</h4>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  ...[more]

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