Peterson Sabrina, Bigler Jeannette, Horner Neilann K, Potter John D, Lampe Johanna W
Interdisciplinary Graduate Program in Nutritional Sciences, Department of Epidemiology, University of Washington, Seattle, WA, USA.
J Nutr. 2005 May;135(5):1051-5. doi: 10.1093/jn/135.5.1051.
UDP-glucuronosyltransferase (UGT) 1A1 is a conjugating biotransformation enzyme that plays a role in maintaining levels of endogenous compounds (e.g., bilirubin) and handling exogenous compounds, including carcinogens. The UGT1A128 polymorphism results in decreased UGT1A1 promoter activity due to 7 thymine-adenine (TA) repeats instead of the commonly found 6 repeats. Studies indicate that foods from the botanical families Cruciferae (e.g., broccoli), Rutaceae (citrus), Liliaceae (e.g., onions), and Leguminosae (legumes) may increase UGT activity. We investigated, in an observational study, whether foods from these botanical groups were associated with increased UGT1A1 activity as indicated by serum bilirubin concentrations and whether the effect varied by UGT1A128 genotype, comparing those homozygous for the TA-repeat allele (7/7) to homozygous wild-types (6/6) and heterozygotes (6/7) combined. Healthy volunteers completed 3-d food records. Blood samples were drawn for genomic DNA collection and bilirubin measures. For total, direct, and indirect bilirubin measures, there was no significant association with any botanical group independently. There was a significant inverse association between all 3 bilirubin measures and interaction of UGT1A1*28 genotype with Cruciferae intake (P < 0.02 for each measure); individuals with the 7/7 genotype had reduced bilirubin concentrations with increased intake of cruciferous vegetables, whereas individuals with the 6/6 or 6/7 genotype did not. With regard to UGT1A1-conjugated carcinogens (e.g., heterocyclic amines, polycyclic aromatic hydrocarbons), individuals with decreased UGT1A1 activity due to the 7/7 genotype may be at greater risk for carcinogenesis, but our results imply that they also may have greater opportunity to decrease that risk through dietary intervention.
尿苷二磷酸葡萄糖醛酸基转移酶（UGT）1A1是一种结合生物转化酶，在内源性化合物（如胆红素）水平维持及外源性化合物（包括致癌物）处理过程中发挥作用。UGT1A128多态性导致UGT1A1启动子活性降低，原因是存在7个胸腺嘧啶-腺嘌呤（TA）重复序列，而非常见的6个重复序列。研究表明，十字花科（如西兰花）、芸香科（柑橘类）、百合科（如洋葱）和豆科（豆类）植物家族的食物可能会增加UGT活性。在一项观察性研究中，我们调查了这些植物类群的食物是否与血清胆红素浓度所表明的UGT1A1活性增加有关，以及这种影响是否因UGT1A128基因型而异，将TA重复等位基因纯合子（7/7）与纯合野生型（6/6）以及杂合子（6/7）组合进行比较。健康志愿者完成了3天的食物记录。采集血样用于基因组DNA收集和胆红素测量。对于总胆红素、直接胆红素和间接胆红素测量，与任何植物类群单独均无显著关联。所有3种胆红素测量值与UGT1A1*28基因型与十字花科蔬菜摄入量的相互作用之间存在显著负相关（每种测量值P<0.02）；7/7基因型个体随着十字花科蔬菜摄入量增加，胆红素浓度降低，而6/6或6/7基因型个体则不然。关于UGT1A1结合的致癌物（如杂环胺、多环芳烃），由于7/7基因型导致UGT1A1活性降低的个体可能发生癌变的风险更高，但我们的结果表明，他们也可能有更大机会通过饮食干预降低该风险。
