2019
DOI: 10.1002/cpt.1304
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss‐of‐function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

5
190
3
4

Year Published

2019
2019
2023
2023

Publication Types

Select...
6
1

Relationship

3
4

Authors

Journals

citations
Cited by 424 publications
(202 citation statements)
references
References 39 publications
5
190
3
4
Order By: Relevance
“…The international population databases show that the frequency of the mutations that reduce the functional activity of the enzyme, such as those described by the PharmVar Consortium, exceeds 1% only in Asians, Latin American and Amerindian populations [14,15,25]. The most frequent mutations of these groups include the rs116855232 variant, either in isolation or combined with rs1272632214.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The international population databases show that the frequency of the mutations that reduce the functional activity of the enzyme, such as those described by the PharmVar Consortium, exceeds 1% only in Asians, Latin American and Amerindian populations [14,15,25]. The most frequent mutations of these groups include the rs116855232 variant, either in isolation or combined with rs1272632214.…”
Section: Discussionmentioning
confidence: 99%
“…A C>T transition in the rs116855232 (p.Arg139Cys) variant is assigned to two haplotypes (NUDT15 � 2 and NUDT15 � 3), which present an extreme loss of gene function, associated with the presence of the T allele of this polymorphism. The T allele of rs116855232 is found more commonly in East Asian [13], Latin [14] and Native American [15] populations, but is rare in populations from Europe, Africa, and South Asia.…”
Section: Introductionmentioning
confidence: 99%
“…The population in our study was not randomly selected since all were subjects for thiopurine treatment. However, since the natural function of TPMT, strangely enough, is still unknown, only individuals on thiopurine treatment are suffering from defective TPMT enzyme [19,47] and consequently this group is the most relevant to study. Although, disease or treatment could influence the results of TPMT enzyme activity measurement (chapter 5.3) and these are, together with high labor intensity and costs, the largest disadvantages of phenotyping.…”
Section: Discussionmentioning
confidence: 99%
“…Implementation into clinical pharmacogenetic routine testing is not very expanded. Most used and recommended today is testing of TPMT, NUDT15 [19] (both used in thiopurine treatment, described in chapter 1.3) and UGT1A1 (treatment with irinotecan, used against, e.g., metastatic colon cancer). Other drugs where pharmacogenetic testing have been proposed or recommended are warfarin (up to 40% of the variation in drug response between individuals are reported to come from the VKORC1 and CYP2C9 genotypes) and tamoxifen [6] (the proportion of CYP2D6 poor metabolizers is up to 12% in some populations whereas ultra-rapid phenotype frequencies are up to 29% of other populations) [13].…”
Section: Brief Overview Of the Pharmacogenetic Field Todaymentioning
confidence: 99%
See 1 more Smart Citation