Martínez Alfonso, Márquez Ana, Mendoza JuanLuis, Taxonera Carlos, Fernández-Arquero Miguel, Díaz-Rubio Manuel, de la Concha Emilio G, Urcelay Elena
Department of Immunology, Hospital Universitario San Carlos, Madrid, Spain.
Inflamm Bowel Dis. 2007 Dec;13(12):1484-7. doi: 10.1002/ibd.20252.
The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case-control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population.
Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at -25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CD patients and compared with 550 ethnically matched controls.
The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; chi(2) = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; chi(2) = 17.04), mainly due to the presence of a risk haplotype (rs3814055T//rs6784598C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20-2.30). Patients with extensive UC carrying the -25385T allele showed increased susceptibility compared with left-sided colitis patients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the -25385T risk allele (P = 0.005).
Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.
孕烷X受体基因（PXR/NR1I2）最近被认为与炎症性肠病（IBD）风险增加有关，尽管随后的一项病例对照研究未能在独立人群中重现最初的关联。这种核受体调节肝脏和肠道中参与解毒过程的基因，如ABCB1/MDR1。溃疡性结肠炎（UC）患者结肠中的PXR表达显著降低，但在克罗恩病（CD）患者中未受影响。考虑到先前的结果，我们旨在研究该基因座对西班牙人群IBD易感性的影响。
在365例UC患者和331例CD患者中分析了三种PXR多态性，包括在初始研究中与IBD风险相关性更强的位于-25385C/T（rs3814055）的一种以及由它们组成的6种单倍型，并与550名种族匹配的对照进行比较。
UC患者和CD患者之间的总体单倍型分布存在显著差异（P = 0.05；χ² = 10.84）。在UC患者中，广泛性结肠炎患者与对照之间存在显著差异（P = 0.004；χ² = 17.04），主要是由于存在一种风险单倍型（rs3814055T//rs6784598C//rs2276707*C：P = 0.001；比值比[OR] = 1.66，95%置信区间[CI] 1.20 - 2.30）。携带-25385T等位基因的广泛性UC患者与左侧结肠炎患者及健康受试者相比，易感性增加。在广泛性UC患者中，位于第3内含子的MDR1 G/A变化（rs3789243）的基因型分布在-25385T风险等位基因携带者/非携带者之间存在显著差异（P = 0.005）。
我们的数据似乎支持PXR基因座与广泛性UC的关联以及PXR和MDR1基因之间的相互作用。
