In vitro characterization of four novel non-functional variants of the thiopurine S-methyltransferase

Epistatic interactions between thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) variations determine 6-mercaptopurine toxicity in Indian children with acute lymphoblastic leukemia

“…TPMT rs2842949 is relatively unexplored, and no data are available to corroborate with leucopenia in other ethnic groups. In the current study, all the variants of this polymorphism showed homozygous mutant phenotype at TPMT*12 C→T, which was earlier reported to decrease the specific activity of TPMT by 50% [31,32]. A study by McLeod et al observed that 11.6% of ALL children from UK had a variant TPMT allele at the 238, 460, or 719 nucleotides at the TPMT locus, which was higher than the frequency observed in our study, suggesting ethnic variations in TPMT allele distribution [17].…”

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…Many TPMT variants have been identified, with TPMT*2, *3A, *3B, and *3C being responsible for most cases of TPMT deficiency (Krynetski et al, 1995;Szumlanski et al, 1996;Tai et al, 1996;Otterness et al, 1997Otterness et al, , 1998; Spire-Vayron de la Moureyre et al, 1998;Hon et al, 1999;Colombel et al, 2000;Hamdan-Khalil et al, 2003;Schaeffeler et al, 2003Schaeffeler et al, , 2004Lindqvist et al, 2004). TPMT*3A is the most common variant in Caucasians (Yates et al, 1997;Collie-Duguid et al, 1999), whereas *3C is the most frequent mutation in those of African (Ameyaw et al, 1999;Hon et al, 1999) or East or Southeast Asian origin CollieDuguid et al, 1999;Kumugai et al, 2001;Chang et al, 2002).…”

The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia

“…Accordingly, TPMT gene contains several polymorphisms most of which occur as nonsynonymous SNPs in the open reading frame of the gene that alter the encoded amino acid sequence and finally lead to enhanced protein degradation [10]. So far, at least 23 SNP in TPMT gene associated with altered TPMT activity have been identified [11][12][13][14]. Among the defective alleles, more than 80% of all low activity cases are attributed to three inactivating mutations (G238C, G460A, and A719G) that characterize the four defective alleles namely TPMT*2, 3B, *3C, and *3A [15].…”