title: A new thiopurine s-methyltransferase haplotype associated with intolerance to azathioprine.
abstract: The authors have analyzed single nucleotide polymorphisms in the thiopurine S-methyltransferase (TPMT) gene in the context of efficacy and toxicity of azathioprine (AZA) to determine possible genotype-phenotype correlations between TPMT allelic variants and response to AZA treatment in 76 Italian patients with myasthenia gravis. They confirm known intronic and exonic TPMT polymorphisms that do not correlate with AZA responses and demonstrate a novel intronic polymorphism in a patient intolerant to AZA. Most importantly, they show that of the 22 AZA-intolerant patients, all 5 who carried mutations of the intolerance-linked haplotype TPMT*3A also carried the intronic T140+114A (rs3931660), all 3 mutations being part of a new haplotype designated TMPT*3E. TPMT*3E was not observed in unresponsive or responsive patients. The association of TPMT*3E with AZA intolerance and its frequency must be ascertained in larger, ethnically different cohorts. Nevertheless, in view of the highly significant association (Psim = 0.0026) between TPMT*3E and AZA intolerance in the study, this new haplotype should be taken into consideration in pharmacogenetic profiling for AZA.
authors: Neurology IV, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors: Lara
authors: L
authors: Colleoni
authors: Dimos
authors: D
authors: Kapetis
authors: Lorenzo
authors: L
authors: Maggi
authors: Giorgia
authors: G
authors: Camera
authors: Eleonora
authors: E
authors: Canioni
authors: Paola
authors: P
authors: Cavalcante
authors: Nicole
authors: N
authors: Kerlero de Rosbo
authors: Fulvio
authors: F
authors: Baggi
authors: Carlo
authors: C
authors: Antozzi
authors: Paolo
authors: P
authors: Confalonieri
authors: Renato
authors: R
authors: Mantegazza
authors: Pia
authors: P
authors: Bernasconi
mesh_terms: D001379:Azathioprine / Q000009:adverse effects*; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007558:Italy; D008780:Methyltransferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine