Kataoka Ryuji, Kimata Akiko, Yamamoto Kanami, Hirosawa Naoko, Ueyama Jun, Kondo Takaaki, Okada Rieko, Kawai Sayo, Hishida Asahi, Naito Mariko, Morita Emi, Wakai Kenji, Hamajima Nobuyuki
Medical Student of Nagoya University School of Medicine, Nagoya, Japan.
Nagoya J Med Sci. 2011 Feb;73(1-2):33-40.
Bilirubin is glucoronized by uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) mainly in the liver, and excreted into bile. The conjugated form is metabolized into the unconjugated form, and then into urobilinogen by bacteria in the intestine. Unconjugated bilirubin and urobilinogen are absorbed into the blood stream. The kidney filtrates conjugated bilurubin and urobilinogen into urine. Accordingly, the reduced enzyme activity of UGTIAI may decrease serum conjugated bilirubin levels, resulting in a lower frequency of positive results of urine bilirubin and urobilinogen. This study examined the associations of UGTIAI Gly71Arg (UGTIAI *6) with urine bilirubin and urobilinogen, as well as serum AST, ALT and GGT. Subjects were 5,172 inhabitants 35 to 69 years old who participated in a cohort study in Nagoya from June 2008 to May 2010. Among them, data from 5,151 participants (1,465 males and 3,686 females) were available for analysis. The age-sex-adjusted odds ratio (OR) of ArgArg relative to GlyGly was 1.37 (95% confidence interval (95% CI), 0.55-1.23) for bilirubin, and 1.67 (95% CI, 0.86-3.26) for urobilinogen. Those of ArgArg+ArgGly were 0.87 (95% CI, 0.59-1.27) and 1.50 (95% CI, 1.17-1.94), respectively. AST, ALT and GGT levels had no associations with the genotype. Although the significant association for urobilinogen was contrary to the biological expectation, this study indicated that UGTIA1 Gly71Arg may be a genetic factor of urine urobilinogen.
胆红素主要在肝脏中由尿苷二磷酸 - 葡糖醛酸基转移酶1A1（UGT1A1）进行葡糖醛酸化，并排泄到胆汁中。结合形式被代谢为非结合形式，然后在肠道中被细菌代谢为尿胆原。非结合胆红素和尿胆原被吸收进入血流。肾脏将结合胆红素和尿胆原滤入尿液。因此，UGT1A1酶活性降低可能会降低血清结合胆红素水平，导致尿胆红素和尿胆原阳性结果的频率降低。本研究调查了UGT1A1 Gly71Arg（UGT1A1 *6）与尿胆红素、尿胆原以及血清AST、ALT和GGT之间的关联。研究对象为2008年6月至2010年5月在名古屋参加队列研究的5172名35至69岁的居民。其中，5151名参与者（1465名男性和3686名女性）的数据可用于分析。相对于GlyGly，ArgArg的年龄 - 性别调整优势比（OR）对于胆红素为1.37（95%置信区间（95%CI），0.55 - 1.23），对于尿胆原为1.67（95%CI，0.86 - 3.26）。ArgArg + ArgGly的OR分别为0.87（95%CI，0.59 - 1.27）和1.50（95%CI，1.17 - 1.94）。AST、ALT和GGT水平与基因型无关联。尽管尿胆原的显著关联与生物学预期相反，但本研究表明UGT1A1 Gly71Arg可能是尿胆原的一个遗传因素。
