Analysis of thiopurine S-methyltransferase phenotype-genotype in a Tunisian population with Crohn's disease.

Abstract

This study was conducted to investigate the thiopurine S-methyltransferase TPMT activity distribution and gene mutations in Tunisian population with positive diagnostic for Crohn's disease. TPMT activity was measured in Tunisian population (n = 88) by a high performance liquid chromatography assay. Polymerase chain reaction-based methods were used to determine the frequency of TPMT mutant alleles TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. TPMT activity was normally distributed, ranging from 4.58 to 35.27 nmol/(h ml) RBC with a mean of 18.67 ± 7.10 nmol/(h ml) RBC. Seven TPMT*3A heterozygotes and one TPMT*3C homozygote were found in 88 patients, with allele frequencies of 0.039 and 1.13, respectively. TPMT*3A and the TPMT*3C, which cause the largest decrease in enzyme activity, were both variant alleles detected in the Tunisian population.

• Authors: Lynda Ben Salah, Mouna Belkhiria el Haj Amor, Chahra Chbili, Saida Khlifi, Neila Fathallah, Iheb Bougmiza, Elhem Ben Jazia, Nicole Houdret, Chaker Ben Salem, Saad Saguem
• Journal: European journal of drug metabolism and pharmacokinetics (Eur J Drug Metab Pharmacokinet) Vol. 38 Issue 4 Pg. 241-4 (Dec 2013) ISSN: 0378-7966 [Print] France
• PMID: 23553048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• DNA
• Methyltransferases
• thiopurine methyltransferase
• Azathioprine

Topics

• Alleles
• Azathioprine (pharmacokinetics)
• Crohn Disease (enzymology, epidemiology, genetics)
• DNA (biosynthesis, genetics)
• Erythrocytes (enzymology)
• Female
• Gene Frequency
• Genotype
• Humans
• Immunosuppressive Agents (pharmacokinetics)
• Male
• Methyltransferases (genetics, metabolism)
• Phenotype
• Tunisia (epidemiology)