Abstract | BACKGROUND: METHODS: RESULTS: The assay was linear to 3 mmol/L IMP [approximately 500 micromol/(g Hb x h)] with a lower limit of quantification of 4 micromol/L [approximately 0.5 micromol/(g Hb x h)]. With IMP-enriched samples, within- and between-day imprecision was < or = 3.6% and < or = 4.9%, respectively, and the inaccuracy was < or = 5.2%. With pooled erythrocytes, within- and between-day imprecision was 3.8% and 7.5%, respectively. ITPA activity in 130 healthy controls was between < 0.5 and 408 micromol IMP/(g Hb x h). Mutant allele frequencies were 0.062 (94C>A) and 0.131 (IVS2 + 21A>C). When we used a cutoff of 125 micromol IMP/(g Hb x h), phenotyping detected all 94C>A mutant cases, all 94C>A and IVS2 + 21A>C compound heterozygotes, all IVS2 + 21A>C homozygotes, and 6 of 24 IVS2 + 21A>C heterozygote-only cases. A novel IVS2 + 68T>C mutation was also found. CONCLUSIONS: The HPLC procedure provides an excellent ITPA phenotype-genotype correlation and led to the discovery of a novel IVS2 + 68T>C mutation. The method could facilitate investigation of the role of ITPA activity for drug toxicity during thiopurine therapy.
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Authors | Maria Shipkova, Kristin Lorenz, Michael Oellerich, Eberhard Wieland, Nicolas von Ahsen |
Journal | Clinical chemistry
(Clin Chem)
Vol. 52
Issue 2
Pg. 240-7
(Feb 2006)
ISSN: 0009-9147 [Print] England |
PMID | 16384889
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Chromatography, High Pressure Liquid
- Erythrocytes
(enzymology)
- Female
- Gene Frequency
- Genotype
- Humans
- Male
- Mutation
- Phenotype
- Pyrophosphatases
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- White People
(genetics)
- Inosine Triphosphatase
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