{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:40:21Z","timestamp":1773200421530,"version":"3.50.1"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract:<\/jats:title>\n          <jats:p>Thiopurine-S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) are crucial enzymes involved in the metabolism of thiopurine drugs. Significant interethnic variation in the expression of <jats:italic toggle=\"yes\">TPMT<\/jats:italic> and <jats:italic toggle=\"yes\">ITPA<\/jats:italic> is caused by single nucleotide polymorphisms of genes encoding these proteins. The aim of this study was to describe the distribution of <jats:italic toggle=\"yes\">TPMT<\/jats:italic> and <jats:italic toggle=\"yes\">ITPA<\/jats:italic> polymorphisms in healthy Tunisian subjects and to establish the metabolizer status of thiopurine drugs in this population. A total of 309 healthy Tunisian subjects were recruited among blood donors of Fattouma Bourguiba Hospital of Monastir. A written informed consent was obtained from all subjects. Whole blood samples were collected from every subject in ethylenediaminetetraacetic acid tubes. <jats:italic toggle=\"yes\">TPMT<\/jats:italic> (c.238 G &gt; C, c.460 G &gt; A and c.719A &gt; G) and <jats:italic toggle=\"yes\">ITPA<\/jats:italic> (c.94C &gt; A and IVS2+21A &gt; C) mutations were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The observed frequencies of <jats:italic toggle=\"yes\">TPMT*3A<\/jats:italic> and <jats:italic toggle=\"yes\">TPMT*3C<\/jats:italic> alleles were both 0.8%. The phenotype distribution of <jats:italic toggle=\"yes\">TPMT<\/jats:italic> was bimodal: 96.8% of subjects were extensive metabolizers and 3.2% were intermediate metabolizers. Genotyping of <jats:italic toggle=\"yes\">ITPA<\/jats:italic> revealed frequencies of 9% and 3% for IVS2+21A &gt; C and c.94C &gt; A mutations, respectively. Accordingly, a trimodal phenotype distribution was found: 75.4% of the subjects were extensive metabolizers, 23.4% were intermediate metabolizers, and 1.2% wereslow metabolizers. Combination of <jats:italic toggle=\"yes\">TPMT<\/jats:italic> and <jats:italic toggle=\"yes\">ITPA<\/jats:italic> genotyping has revealed that a quarter of the Tunisian Population carries polymorphisms that reduce the metabolic activities of these enzymes.<\/jats:p>","DOI":"10.1097\/ftd.0000000000000548","type":"journal-article","created":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T22:18:38Z","timestamp":1533248318000},"page":"655-659","source":"Crossref","is-referenced-by-count":8,"title":["Distribution of Genetic Polymorphisms of Genes Implicated in Thiopurine Drugs Metabolism"],"prefix":"10.1097","volume":"40","author":[{"given":"Zohra","family":"Chadli","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emna","family":"Kerkeni","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibtissem","family":"Hannachi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saoussen","family":"Chouchene","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Ben Fredj","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naceur A.","family":"Boughattas","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karim","family":"Aouam","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, Monastir, Tunisia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amel","family":"Chaabane","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, University Hospital;"},{"name":"Pharmacology Department, Faculty of Medicine, University of Monastir, 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