Department of Medical, Viborg Regional Hospital, 8800 Viborg, Denmark.
World J Gastroenterol. 2011 Jan 14;17(2):197-206. doi: 10.3748/wjg.v17.i2.197.
To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD).
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.
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).
Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.
探讨核受体多态性在炎症性肠病（IBD）发病风险中的作用。
在丹麦的一项克罗恩病（CD）患者 327 例、溃疡性结肠炎（UC）患者 495 例和健康对照者 779 例的病例对照研究中，检测了核因子（NF）-κB（NFKB1）NFκB-94ins/del（rs28362491）、过氧化物酶体增殖物激活受体（PPAR）-γ（PPARγ）PPARγPro12Ala（rs1801282）和 C1431T（rs3856806）、妊娠相关蛋白 X 受体（PXR）（NR1I2）PXR A-24381C（rs1523127）、C8055T（2276707）和 A7635G（rs6785049）以及肝 X 受体（LXR）（NR1H2）LXR T-rs1405655-C 和 T-rs2695121-C 多态性。采用 logistic 回归模型估计比值比（OR）和 95%可信区间（CI）。
与相应的纯合野生型基因型相比，PXR A7635G 变异型、PPARγ Pro12Ala 和 LXR T-rs2695121-C 纯合变异型基因型与 UC 发病风险相关（OR：1.31，95%CI：1.03-1.66，P=0.03；OR：2.30，95%CI：1.04-5.08，P=0.04；OR：1.41，95%CI：1.00-1.98，P=0.05）。在从不吸烟者中，PXR A7635G 和 LXR T-rs1405655-C 和 T-rs2695121-C 变异型基因型与 IBD 发病风险相关（OR：1.41，95%CI：1.05-1.91，P=0.02；OR：1.63，95%CI：1.21-2.20，P=0.001；OR：2.02，95%CI：1.36-2.99，P=0.0005）。与相应的纯合变异型基因型相比，PXR A7635G（rs6785049）变异型基因型与 UC 发病年龄<40 岁和广泛性疾病的风险增加相关（OR：1.34，95%CI：1.03-1.75；OR：2.49，95%CI：1.24-5.03）。
常见的 PXR 和 LXR 多态性可能与 IBD 的发病风险相关，尤其是在从不吸烟者中。
