AbstractBackground:Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy.Methods:NUDT15 and TPMT genotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique.Results:Of 370 samples received for TPMT testing, 206 samples were available for NUDT15 genotyping. The NUDT15 risk allele frequency was 10.7%, with the frequency of wild, heterozygous and mutant genotypes being 80.6%, 17.5% and 1.9%, respectively. TPMT variants were seen in 13 of 370 (3.5%) patients, whereas the NUDT15 variant was seen in 40 of 206 (19.4%) patients. Thiopurine-induced toxicity information was available for 101 patients, among whom 10 developed leukopenia and all harbored the NUDT15 variant (p<0.0001). NUDT15 was clinically more relevant than TPMT in terms of sensitivity and specificity, as well as with a statistically significant difference in thiopurine dose requirement for patients with the NUDT15 variant.Conclusions:A preemptive NUDT15 genotyping approach can therefore help identify high-risk patients (NUDT15 C415T positive) who could benefit from thiopurine dose reduction, thereby preventing fatal thiopurine-induced toxicity.
Drug Metabolism and Drug Interactions – de Gruyter
Published: Mar 28, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera