Thiopurine S-methyltransferase (TPMT) pharmacogenetics: three new mutations and haplotype analysis in the Estonian population

Tamm, Riin; Oselin, Kersti; Kallassalu, Kristi; Mägi, Reedik; Anier, Kaili; Remm, Maido; Metspalu, Andres

doi:10.1515/cclm.2008.187

Cited by 17 publications

(8 citation statements)

References 32 publications

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“…A further comparison of our results with those in other ethnic groups also revealed some similarities to other ethnic populations. Specifically, the frequencies for the CYP2C19*2 in our study are comparable to those in the Romanian (0.12), Lebanese (0.13),[60] Turkish (0.12),[61–63] Jewish (0.15),[23] Russian (0.11)[64] and Italian (0.12),[65] but slightly lower than those in the Chinese (0.25),[66,67] North Indian (0.26)[68] and Thai (0.29) populations [22]…”

Section: Discussionsupporting

confidence: 57%

Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population

Tayeb

Bakheet

Zaza

et al. 2015

Journal of Pharmacy and Pharmacology

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Section: Discussionsupporting

confidence: 57%

Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population

Tayeb

Bakheet

Zaza

et al. 2015

Journal of Pharmacy and Pharmacology

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“…The frequency of patients with TPMT variants is much higher among Caucasians (8.1-10.1%) than in Asian populations (2.3-4.2%) [3][4][5][6][7][8]. In studies carried out in various ethnic groups, the predominant variants identified were TPMT*3C, TPMT*3A, and TPMT*2, which accounted for over 95% of inherited TPMT deficiency.…”

mentioning

confidence: 99%

Complete sequence-based screening of TPMT variants in the Korean population

Kim

Lee²,

Lee³

et al. 2015

Pharmacogenetics and Genomics

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Thiopurine S-methyltransferase (TPMT) is a cytoplasmic enzyme involved in the metabolism of thiopurine drugs and its activity is largely influenced by polymorphisms of the TPMT gene. To date, more than 35 TPMT variants are known to be associated with reduced enzyme activity, but most studies on the TPMT genotype have included only common nonfunctional variants, such as TPMT*2 and TPMT*3. In this study, we carried out a complete sequencing analysis to screen all TPMT variants in Korean patients. A total of 900 Korean patients were genotyped for TPMT and 30 patients (3.3%) had the known TPMT variant alleles. TPMT*3C was found in 25 patients (2.8%): 24 patients with TPMT*1/*3 and one with TPMT*3/*3. Rare TPMT variants including TPMT*6, TPMT*16, and TPMT*32 were detected in five patients (0.6%) and a novel variant, TPMT*38 (c.514T>C, p.S172P), was identified in two patients. This is the first complete sequence-based screening study evaluating all TPMT variants in Asian populations.

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“…As might be expected, our analysis revealed some similarities with other ethnic populations in the alterations of a number of variants. Thus, for example, the results point to relatively similar frequencies for the CYP2C19 * 2 (rs4244285) to those in several other ethnic groups, including the Romanian (0.12), Lebanese (0.13) [ 40 ], Turkish (0.12) [ 55 – 57 ], Jewish (0.15%) [ 39 ], Russian (0.11) [ 58 ], and Italian (0.12) [ 59 ], but slightly lower than those in the Chinese (0.25) [ 60 , 61 ], North Indian (0.26) [ 62 ], and Thai (0.29) [ 22 ] populations. We also found low MAFs for CYP2C19 * 2 (0.093) and CYP 2C19 * 3 (0.001) which were comparatively lower than in Africans, while that of the CYP2C19 * 17 (0.256) matched those of the European populations but was higher than those in African and other Asian populations (see also Supplementary Data).…”

Section: Discussionmentioning

confidence: 74%

The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs

et al. 2015

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Background. The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations. Materials and Methods. We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results. Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups. Discussion. The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population.

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Thiopurine S-methyltransferase (TPMT) pharmacogenetics: three new mutations and haplotype analysis in the Estonian population

Abstract: Our results point to several markers that predict reduced enzyme activity. None of the identified markers were associated with high enzyme activity.

Cited by 17 publications

References 32 publications

Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population

Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population

Complete sequence-based screening of TPMT variants in the Korean population

The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs

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