[Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

Zhongguo Fei Ai Za Zhi

Guangdong General Hospital Institute of Lung Cancer, Key Laboratory of Translational Medicine, Medical Research Center, 
Guangdong General Hospital Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Published: December 2017

Background: Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism.

Methods: A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method.

Results: Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype.

Conclusions: Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973388PMC
http://dx.doi.org/10.3779/j.issn.1009-3419.2017.12.04DOI Listing

Publication Analysis

Top Keywords

ugt1a1*28 polymorphism
16
fragment analysis
16
analysis method
12
polymorphism fragment
8
fragment
5
[detection ugt1a1*28
4
polymorphism
4
fragment analysis]
4
analysis] background
4
background uridine-diphosphoglucuronosyl
4

Similar Publications

The association between UGT1A1 polymorphisms and treatment toxicities of liposomal irinotecan.

ESMO Open

February 2023

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Background: Initial dose adjustment is recommended for patients with known UGT1A1∗28 homozygosity for both conventional irinotecan and liposomal irinotecan (nal-IRI). A recent population pharmacokinetic (PK) study showed that Asian patients had a lower prevalence of UGT1A1∗28 homozygosity but a significantly higher maximum blood concentration of SN-38 (SN-38 Cmax) and a higher incidence of grade ≥3 neutropenia after nal-IRI administration than Caucasian patients. The current study investigated the association of UGT1A1 polymorphisms, including the Asian prevalent UGT1A1∗6, PK and toxicities of nal-IRI-based therapy in the Asian population.

View Article and Find Full Text PDF

Background: Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5-8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type.

View Article and Find Full Text PDF

Background/objectives: Gilbert's syndrome (GS) is a hereditary pathology that affects approximately 10% of the world's population. In most cases, GS is associated with the polymorphism of gene coding the enzyme bilirubin uridine diphosphate glucuronosyltransferase (UGT-1A) which plays a key role in the bilirubin metabolism. The presence of an additional TA repeat in the TATA box of the gene promoter (the allelic variant of 7TA, abbreviated as ) leads to a significant decrease in the enzymatic activity of UGT-1A in the liver and to decrease in glucuronidation process as a consequence.

View Article and Find Full Text PDF

Background: Pre-therapeutic UGT1A1 genotyping is not yet routinely performed in most hospitals in patients starting irinotecan chemotherapy. The aim of this position paper was to evaluate the available evidence and to assess the potential value of genotyping of UGT1A1∗28 and UGT1A1*6 in patients before starting treatment with irinotecan to reduce the risk of severe toxicity.

Methods: The literature was selected and assessed based on five pre-specified criteria: 1) the level of evidence for associations between UGT1A1 polymorphisms and irinotecan-induced severe toxicity, 2) clinical validity and utility of pre-therapeutic genotyping of UGT1A1, 3) safety and tolerability of irinotecan in carriers of UGT1A1 polymorphisms, 4) availability of specific dose recommendations for irinotecan in carriers of UGT1A1 polymorphisms, 5) evidence of cost benefits of pre-therapeutic genotyping of UGT1A1.

View Article and Find Full Text PDF
Article Synopsis
  • This study explores the potential for hepatic adaptation in healthy individuals taking therapeutic doses of acetaminophen (APAP), focusing on the incidence of serum alanine aminotransferase (ALT) elevation.
  • Over 28 days, 242 healthy participants were randomly assigned to receive either 3 g/day of APAP or a placebo, with monitoring for liver function and genetic factors related to drug metabolism.
  • Results indicated that 66% of those on APAP were tolerant with normal ALT levels, while 34% were susceptible, with some experiencing spontaneous resolution of elevated ALT levels, classified as adaptation.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!