Comparison of three methods for genotyping the UGT1A1 (TA) n repeat polymorphism

The UGT1A1 promoter contains a (TA) n repeat polymorphism. The 7 repeat allele is associated with decreased enzyme activity and patients homozygous for this allele treated with irinotecan may experience life-threatening toxicity. Here, we have compared three methods [DNA sequencing, fragment analysi...

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Bibliographic Details
Published in:Clinical biochemistry 2007-06, Vol.40 (9), p.710-717
Main Authors: Baudhuin, Linnea M., Highsmith, W. Edward, Skierka, Jennifer, Holtegaard, Leonard, Moore, Brenda E., O'Kane, Dennis J.
Format: Article
Language:English
Subjects:
African Americans - genetics
Alleles
Camptothecin - adverse effects
Camptothecin - analogs & derivatives
Capillary electrophoresis
Fragment analysis
Genotype
Genotyping
Glucuronosyltransferase - genetics
Humans
Irinotecan
Polymerase Chain Reaction - economics
Polymerase Chain Reaction - methods
Polymorphism, Genetic
Promoter Regions, Genetic - genetics
Sequence Analysis, DNA - economics
Sequence Analysis, DNA - methods
Sequencing
TATA box
Time Factors
UGT1A1
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Summary:The UGT1A1 promoter contains a (TA) n repeat polymorphism. The 7 repeat allele is associated with decreased enzyme activity and patients homozygous for this allele treated with irinotecan may experience life-threatening toxicity. Here, we have compared three methods [DNA sequencing, fragment analysis, and the Invader® assay (Third Wave Technologies)] for genotyping this polymorphism. All of the DNA samples ( n = 119) had concordant genotype calls between the sequencing and size-based methods. The Invader® method was also concordant if the genotypes were 6/6, 6/7, or 7/7. Both the size-based method and the Invader® method had straightforward data analysis, while interpretation of the sequencing results was occasionally more challenging. The Invader® method required more concentrated DNA for analysis, was more expensive, and had a limited genotyping spectrum. All three methods were valuable for genotyping the UGT1A1 (TA) n repeat, with the sequencing and size-based assays having the fewest drawbacks.
ISSN:0009-9120
1873-2933
DOI:10.1016/j.clinbiochem.2007.03.007