Hodgkin lymphoma is a highly curable malignancy, but treatment outcome might be influenced by inherited gene polymorphisms determining anticancer agent metabolism. We prospectively collected peripheral blood lymphocytes from 313 patients with Hodgkin lymphomas to analyze GSTP1, GSTM1, GSTT1, UGT1A1, and CYP3A4 enzyme gene polymorphisms. All patients were treated with chemotherapy, associated wi...

High levels of unconjugated bilirubin (UCB) in newborn children is associated with a reduction in hepatic UDP glucuronosyltransferase (UGT) 1A1 activity that can lead to CNS toxicity, brain damage, and even death. Little is known regarding those events that lead to UCB accumulation in brain tissue, and therefore, we sought to duplicate this condition in mice. The human UGT1 locus, encoding all ...

Nilotinib potently inhibits human uridine diphosphate-glucuronosyltransferase (UGT1A1) activity, causing hyperbilirubinemia. We investigated the influence of UGT1A1 polymorphisms and nilotinib plasma trough concentrations (C0) on nilotinib-induced hyperbilirubinemia in 34 Japanese patients with chronic myeloid leukemia (CML). The proportion of patients with hyperbilirubinemia was significantly ...

INTRODUCTION Glucuronidation is an important phase II pathway responsible for the metabolism of many endogenous substances and drugs to less toxic metabolites, which undergo renal excretion. The aim of the current work was to evaluate genotype and allele frequencies of certain UDP-glucuronosyltransferase 1A1 (UGT1A1) variants in an Arab population. MATERIAL AND METHODS Genomic DNA was isolate...

Transcription of UDP-glucuronosyltransferase (UGT) 1A1 is regulated by the transcription factors, constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucocorticoid receptor (GR), hepatocyte nuclear factor (HNF) 1 alpha, and HNF4 alpha. The purpose of this study was to determine whether the genetic polymorphisms in the RNA polymerase II core promoter and the upstream phenobarbita...

Crigler-Najjar syndrome is a rare autosomal recessive disease caused by mutations in the UGT1A1 gene. These mutations result in the deficiency of UGT1A1, a hepatic enzyme essential for bilirubin conjugation. This report describes the case of a 4-month-old boy with the cardinal symptoms of Crigler-Najjar syndrome type II. Molecular genetic analysis showed a homozygous UGT1A1 promoter mutation [A...

Silymarin is the most commonly used herbal medicine by patients with chronic liver disease. Silymarin flavonolignans undergo rapid first-pass metabolism primarily by glucuronidation. The aims of this investigation were: (1) to determine the association of UGT1A1*28 polymorphism with the area under the plasma concentration-time curves (AUCs) for silybin A (SA) and silybin B (SB); (2) to evaluate...

Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects fro...

Despite the widespread use of the five major xanthophylls astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, ...

BACKGROUND We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TA)nTAA promoter polymorphism in Omani sickle cell anemia (SCA) patients, homozygotes for African (Benin and Bantu) and Arab-Indian β(S) haplotypes, but sharing the same microgeographical environment and comparable life style factors. ...