Allele frequency of inosine triphosphate pyrophosphatase (ITPA) and thiopurine-S-methyl transferase (TPMT) genes in the Tunisian population

Melaouhia, Salma; Fekih, M.; Garat, Anne; Allorge, Delphine; Ferchichi, Henda; Klouz, Anis; Boubaker, J.; Broly, Franck; Lakhal, Mohamed

doi:10.1016/j.clinre.2011.12.001

Cited by 8 publications

(7 citation statements)

References 31 publications

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“…It is notable that the frequency of TPMT mutant alleles found in our study (80%) is much higher than what has been reported in other similar previous studies performed in other ethnic groups,[ 23 24 25 26 32 33 34 ] among Arabs[ 27 28 ] and even among Egyptians. [ 29 30 31 ]…”

Section: Discussioncontrasting

confidence: 79%

“…Among 208 Tunisian subjects, TPMT*3C was the most common mutant allele accounting for 1.44%, followed by TPMT*3B in 0.24% where no TPMT*3A or TPMT* could be found. [ 28 ]…”

Section: Discussionmentioning

confidence: 99%

“…Among 208 Tunisian subjects, TPMT*3C was the most common mutant allele accounting for 1.44%, followed by TPMT*3B in 0.24% where no TPMT*3A or TPMT*2 could be found. [28] Data about TPMT polymorphism in Egypt are scarce. Furthermore, testing of TPMT polymorphism is not a routine work up in Egyptian cancer centers.…”

Section: Discussionmentioning

confidence: 99%

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Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study

El-Rashedy

Ragab

Dawood

et al. 2015

Indian J Med Paediatr Oncol

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Background:6-mercaptopurine (6-MP) is an essential component of pediatric acute lymphoblastic leukemia (ALL) maintenance therapy. Individual variability in this drug-related toxicity could be attributed in part to genetic polymorphism thiopurine methyltransferase (TPMT).Aim:To investigate the frequency of common TPMT polymorphisms in a cohort of Egyptian children with ALL and the possible relation between these polymorphisms and 6-MP with short-term complications.Materials and Methods:This study included 25 children. Data related to 6-MP toxicity during the maintenance phase were collected from the patients’ files. DNA was isolated and genotyping for TPMT G460A, and A719G mutations were performed by polymerase chain reaction-restriction fragment length polymorphism.Results:Twenty (80%) of the included 25 patients had a polymorphic TPMT allele. TPMT*3A was the most frequent (14/25, 56%), 8 patients were homozygous and 6 were heterozygous. TPMT*3C mutant allele was found in 4 patients (16%) in the heterozygous state while 2 patients (8%) were found to be heterozygous for TPMT*3B mutant allele. TPMT mutant patients, especially homozygous, were at greater risk of 6-MP hematological toxicity without significant difference regarding hepatic toxicity.Conclusions:TPMT polymorphism was common among the studied group and was associated with increased risk of drug toxicity. A population-based multi-center study is required to confirm our results.

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Section: Discussioncontrasting

confidence: 79%

“…Among 208 Tunisian subjects, TPMT*3C was the most common mutant allele accounting for 1.44%, followed by TPMT*3B in 0.24% where no TPMT*3A or TPMT* could be found. [ 28 ]…”

Section: Discussionmentioning

confidence: 99%

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Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study

El-Rashedy

Ragab

Dawood

et al. 2015

Indian J Med Paediatr Oncol

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“…Altered TPMT activity predominantly results from single nucleotide polymorphisms. The wild-type allele is designated as TPMT*1 and three alleles designated as TPMT*2 (c.238 G>C), TPMT*3A (c.460 G>A & c.719 A>G) ( 9 ), and TPMT*3C (c.719 A>G) ( Fig. 1 ) account for about 95% of intermediate or low enzyme activity cases ( 11 – 15 ).…”

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confidence: 99%

Polymorphisms of the thiopurine S-methyltransferase gene among the Libyan population

Zeglam

Benhamer

Aboud

et al. 2015

Libyan Journal of Medicine

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BackgroundThiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S-methylation of 6-mercaptopurine and azathioprine. Low activity phenotypes are correlated with polymorphism in the TPMT gene. Patients with low or undetectable TMPT activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. Since ethnic differences in the TPMT gene polymorphism have been demonstrated worldwide, assessing it in the Libyan population is worthwhile.MethodsWe investigated TPMT gene polymorphism in a total of 246 Libyan healthy adult blood donors from three different Libyan regions (Tripoli, Yefren, and Tawargha) and 50 children with acute lymphoblastic leukaemia (ALL). We used polymerase chain reaction restriction length polymorphism (PCR-RFLP) and allele-specific PCR-based assays to analyse the TPMT gene for the variants *2 c.238 G>C, *3A (c.460 G>A and c.719 A>G), *3B (c.460 G>A), and *3C (c.719 A>G).ResultsOur results show that the TPMT variants associated with low enzymatic activity were detected in 3.25% (8 in 246) of adult Libyan individuals and the frequency of total mutant alleles was 1.63%. Heterozygous genotypes were TPMT*3A in three subjects (0.61%) and TPMT*3C in five subjects (1.02%). No TPMT*2 and TPMT*3B allelic variants and no homozygous or compound heterozygous mutant alleles were detected. The normal allele (wild-type) was found in 98.4% of the adult individuals studied. No mutant alleles were detected among the 50 children who had ALL.ConclusionsWe report on the presence of the TPMT*3C and *3A mutant alleles in the Libyan population. Therefore, monitoring the patients to be treated with doses of thiopurine drugs for TPMT variants is worthwhile to avoid the development of severe myelosuppression.

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“…ITPA gene DNA sequence was amplified by routine PCR using mismatched primers to create an XmnI restriction sites as described elsewhere [10].…”

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confidence: 99%

ITPA gene variant may protect against anemia induced during pegylated interferon Alfa and Ribavirin combination treatment in Ukrainian patients with chronic hepatitis C

Kucherenko

Pampukha

Bobrova³

et al. 2015

Cytol. Genet.

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Allele frequency of inosine triphosphate pyrophosphatase (ITPA) and thiopurine-S-methyl transferase (TPMT) genes in the Tunisian population

Cited by 8 publications

References 31 publications

Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study

Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study

Polymorphisms of the thiopurine S-methyltransferase gene among the Libyan population

ITPA gene variant may protect against anemia induced during pegylated interferon Alfa and Ribavirin combination treatment in Ukrainian patients with chronic hepatitis C

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