Related Experiment Video

Updated: Mar 10, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.4K

The impact of the UGT1A1*60 allele on bilirubin serum concentrations

Amy L Pasternak1, Kristine R Crews1, Kelly E Caudle1

  • 1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.

Pharmacogenomics
|December 15, 2016
PubMed

Insights

The uridine-diphosphate glucuronyl transferase 1A1 (UGT1A1) -3279T>G (*60) variant is not linked to higher bilirubin levels in children. This finding impacts understanding of UGT1A1 genetic variations and bilirubin metabolism.

Area of Science:

  • Pharmacogenomics
  • Genetics
  • Biochemistry

Background:

  • The UGT1A1 gene plays a crucial role in bilirubin metabolism.
  • Genetic variations in UGT1A1, such as the -3279T>G (*60) variant, can affect enzyme activity.
  • Understanding these variations is important for predicting drug responses and disease risk.

Purpose of the Study:

  • To determine the functional impact of the UGT1A1 -3279T>G (*60) variant on serum bilirubin concentrations.
  • To investigate the association between the UGT1A1 -3279T>G (*60) variant and bilirubin levels in pediatric patients.
  • To assess the linkage disequilibrium between the UGT1A1 -3279T>G (*60) and A(TA)7TAA (*28) variants.

Main Methods:

  • Retrospective review of serum bilirubin concentrations in pediatric patients.
  • Genotyping for UGT1A1 -3279T>G (*60) and A(TA)7TAA (*28) variants.
  • Statistical analysis to evaluate associations and linkage disequilibrium.

Main Results:

  • No significant difference in total bilirubin concentration was observed between patients with UGT1A1*1/*1 and UGT1A1*60/*60 genotypes.
  • Total bilirubin concentrations were lower in patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant compared to those homozygous for the A(TA)7TAA (*28/*28) variant (p < 0.01).
  • Strong incomplete linkage disequilibrium was found between the -3279T>G (*60) and A(TA)7TAA (*28) variants in both black and white populations.

Conclusions:

  • The UGT1A1 -3279T>G (*60) variant is not associated with elevated serum bilirubin concentrations.
  • The findings suggest that the *60 variant may have a different functional impact than previously assumed.
  • Further research is needed to fully elucidate the role of this variant in bilirubin metabolism and clinical outcomes.
Abstract

Keywords:
*60UGT1A1pharmacogenomics

More Related Videos

Using 2-Photon Microscopy to Quantify the Effects of Chronic Unilateral Ureteral Obstruction on Glomerular Processes11:47

Using 2-Photon Microscopy to Quantify the Effects of Chronic Unilateral Ureteral Obstruction on Glomerular Processes

Published on: March 4, 2022

2.7K
A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants06:35

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

Published on: October 10, 2022

2.5K

Related Concept Videos

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
52
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
85
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
80
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
60
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
246
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
81