Role of the PXR gene locus in inflammatory bowel diseases
Role of the PXR gene locus in inflammatory bowel diseases
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DOI：
10.1002/ibd.20252
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发表时间：
2007-12-01
影响因子：
4.9
通讯作者：
Urcelay, Elena
中科院分区：
文献类型：
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作者：
Martinez, Alfonso;Marquez, Ana;Urcelay, Elena
背景：妊娠X受体基因（PXR/NRII2）最近与炎症性肠病（IBD）风险增加有关，尽管随后的病例对照研究未能在独立人群中复制原始关联。这种核受体调节参与肝脏和肠道解毒过程的基因，如ABCBI/MDR1。溃疡性结肠炎（UC）患者结肠中PXR表达明显降低。但对克罗恩病（CD）患者没有影响。考虑到以前的结果。我们的目的是调查这个基因座对西班牙人群IBD易感性的影响。方法：分析365例UC和331例CD患者的3个PXR多态性，其中1个与IBD风险在-25385C/T位点（rs3814055）的相关性更强，以及它们符合的6个单倍型，并与550个种族匹配的对照进行比较。结果：UC与CD患者整体单倍型分布差异有统计学意义（P = 0.05; X-2 = 10.84）。在UC患者中，广泛结肠炎患者与对照组之间存在显著差异（P = 0.004; X-2 = 17.04），主要是由于存在风险单倍型（rs3814055*T//rs6784598*C// rs2276707*C: P = 0.001：优势比[OR] = 1.66, 95%可信区间[CI] 1.20-2.30）。携带-25385T等位基因的广泛UC患者与左侧结肠炎患者和健康受试者相比，易感性增加。在广泛UC患者中，-25385T风险等位基因携带者和非携带者之间，位于内含子3 （rs3789243）的MDR1 G/ a基因型的分布显著不同（P = 0.005）。结论：我们的数据似乎支持PXR位点与广泛UC的关联以及PXR和MDR1基因之间的相互作用。
Background: The pregnane X receptor gene (PXR/NRII2) 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 ABCBI/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC). but remained unaffected in Crohn's disease (CD) patients. Considening previous results. we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population.Methods: 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 ethnicallv matched controls.Results: The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; X-2 = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; X-2 = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C// 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 leftsided 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).Conclusions: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.