de Souza Marcelo Moreira Tavares, Vaisberg Victor Van, Abreu Rodrigo Martins, Ferreira Aline Siqueira, daSilvaFerreira Camila, Nasser Paulo Dominguez, Paschoale Helena Scavone, Carrilho Flair José, Ono Suzane Kioko
Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
Medicine (Baltimore). 2017 Mar;96(11):e6306. doi: 10.1097/MD.0000000000006306.
Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A128 (UGT1A128). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine-adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A128 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A128 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.
吉尔伯特综合征（GS）是一种常见的良性临床病症，其特征为间歇性非结合性高胆红素血症，主要归因于尿苷二磷酸 - 葡萄糖醛酸基转移酶1A128（UGT1A128）的多态性。有报道称，一名接受丙型肝炎治疗的GS患者出现了高胆红素血症，并且其他UGT同工型多态性与病毒性肝炎的更差预后有关。然而，关于GS对肝病情况的影响知之甚少。我们的目的是评估慢性丙型肝炎（CHC）患者中UGT1A1基因型的频率，并与总胆红素（TB）进行相关性分析。这是在一家大型三级医疗中心进行的病例对照研究。病例为经丙型肝炎病毒（HCV）聚合酶链反应确诊的CHC患者。排除标准为乙型肝炎病毒或人类免疫缺陷病毒（HIV）合并感染。对照为健康献血者。对UGT1A1启动子区域进行基因分型，并获取HCV患者的血清胆红素水平。病例组（n = 585；P = 0.101）和对照组（n = 313；P = 0.795）的基因型和等位基因频率相似。根据基因型中的胸腺嘧啶 - 腺嘌呤重复序列，总胆红素升高（P < 0.001），并且总胆红素大于1mg/dL组的UGT1A128受试者比总胆红素值<1mg/dL组更多（18.3对5.3；P < 0.001）。胆红素水平与所研究的多态性相关，并且这是首次在慢性肝病样本中报告这些发现。在总胆红素水平升高的患者中，UGT1A128的频率高于总胆红素正常的患者。对于GS患者，应考虑在胆红素水平异常或药物代谢方面进行个性化护理。
