*Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; †IBD Clinical and Research Center, ISCARE I.V.F. Lighthouse, Prague, Czech Republic; ‡Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; §Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Prague, Czech Republic; and ‖4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Inflamm Bowel Dis. 2014 Mar;20(3):481-7. doi: 10.1097/01.MIB.0000440817.84251.98.
The oxidative stress is thought to play an important role in Crohn's disease (CD). As serum bilirubin represents the major endogenous antioxidant, this article aimed to evaluate in a clinical study, whether serum bilirubin levels and genes affecting its systemic concentrations are associated with CD.
This exploratory case-control study was based on pediatric (n = 119) and adult (n = 504) patients with CD and 370 appropriate healthy control subjects. The (GT)n and (TA)n dinucleotide variations in heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) gene promoters were determined by fragment analysis. Serum bilirubin levels were compared in a subset of 90 cases and 229 controls, for whom biochemical data were available.
Substantially lower serum bilirubin levels were detected in patients with CD compared with controls (7.4 versus 12.1 μmol/L, P < 10). Serum bilirubin levels were significantly lower in patients with CD within all UGT1A128 genotypes (P < 0.05). UGT1A128 homozygotes with wild-type NOD2 gene variant exhibited significant delay in CD manifestation (P = 0.004), while the protective effect of UGT1A1*28 homozygosity was lost in those patients with mutated NOD2 gene. No associations between CD risk and individual HMOX1 gene variants were observed.
CD is associated with significantly low serum bilirubin levels, most likely as a result of increased oxidative stress accompanying this inflammatory disease. UGT1A1*28 allele homozygosity, responsible for higher bilirubin levels, seems to be an important modifier of CD manifestation.
氧化应激被认为在克罗恩病（CD）中发挥重要作用。由于血清胆红素代表主要的内源性抗氧化剂，本文旨在通过临床研究评估血清胆红素水平及其影响其全身浓度的基因是否与 CD 相关。
本探索性病例对照研究基于儿科（n=119）和成人（n=504）CD 患者和 370 名适当的健康对照者。通过片段分析确定血红素加氧酶 1（HMOX1）和胆红素 UDP-葡糖醛酸基转移酶（UGT1A1）基因启动子中的（GT）n 和（TA）n 二核苷酸变异。在 90 例病例和 229 例对照中比较了血清胆红素水平，这些病例和对照中有生化数据。
与对照组相比，CD 患者的血清胆红素水平明显较低（7.4 与 12.1 μmol/L，P<10）。在所有 UGT1A128 基因型的 CD 患者中，血清胆红素水平均显著降低（P<0.05）。携带野生型 NOD2 基因变异的 UGT1A128 纯合子患者出现 CD 表现的明显延迟（P=0.004），而在 NOD2 基因突变的患者中，UGT1A1*28 纯合子的保护作用丧失。未观察到 CD 风险与单个 HMOX1 基因变异之间存在关联。
CD 与明显较低的血清胆红素水平相关，这很可能是由于这种炎症性疾病伴随的氧化应激增加所致。负责更高胆红素水平的 UGT1A1*28 等位基因纯合子似乎是 CD 表现的重要修饰因子。
