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


CONCLUSIONS
Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.
Department of Medical, Viborg Regional Hospital, 8800 Viborg, Denmark. va9791@gmail.com
Vibeke
V
Andersen
Jane
J
Christensen
Anja
A
Ernst
Bent A
BA
Jacobsen
Anne
A
Tjønneland
Henrik B
HB
Krarup
Ulla
U
Vogel
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D012306:Risk; D012907:Smoking
D000071518:Liver X Receptors; D016328:NF-kappa B; C000605210:NR1H2 protein, human; C000625852:NR1I2 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid
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