Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors? Academic Article uri icon

Overview

abstract

  • To ensure accuracy of UGT1A1 (TA)n (rs3064744) genotyping for use in pharmacogenomics-based irinotecan dosing, we tested the concordance of several commonly used genotyping technologies. Heuristic genotype groupings and principal component analysis demonstrated concordance for Illumina sequencing, fragment analysis, and fluorescent PCR. However, Illumina sequencing and fragment analysis returned a range of fragment sizes, likely arising due to PCR "slippage". Direct sequencing was accurate, but this method led to ambiguous electrophoregrams, hampering interpretation of heterozygotes. Gel sizing, pyrosequencing, and array-based technologies were less concordant. Pharmacoscan genotyping was concordant, but it does not ascertain (TA)8 genotypes that are common in African populations. Method-based genotyping differences were also observed in the publication record (p < 0.0046), although fragment analysis and direct sequencing were concordant (p = 0.11). Genotyping errors can have significant consequences in a clinical setting. At the present time, we recommend that all genotyping for this allele be conducted with fluorescent PCR (fPCR).

publication date

  • January 30, 2020

Research

keywords

  • Genotyping Techniques
  • Glucuronosyltransferase
  • Polymorphism, Genetic

Identity

PubMed Central ID

  • PMC7037496

Scopus Document Identifier

  • 85078978263

Digital Object Identifier (DOI)

  • 10.1002/jcla.21820

PubMed ID

  • 32019188

Additional Document Info

volume

  • 21

issue

  • 3