Frequency of thiopurine methyltransferase mutation in patients of Mediterranean area with inflammatory bowel disease and autoimmune disorders.
OBJECTIVE
Few studies exist on the frequency of thiopurine methyltransferase (TPMT) mutation in patients from Southern Europe. We aimed to evaluate the frequency of TPMT mutation in a homogeneous Sicilian cohort of patients with inflammatory bowel disease (IBD), autoimmune and hematological disorders, the rate of thiopurine-related adverse events, and its association with the TPMT genotype.


RESULTS
Among 105 patients with IBD, 45 with autoimmune disease, and 34 with hematologic diseases, the homozygous TPMT variant genotype was found in one patient only (0.5%), while the heterozygous TPMT genotype was identified in 8 patients (4.3%). In patients with IBD, leukopenia was observed in ten patients: one had the homozygous TPMT genotype, one the heterozygous genotype, and the remaining eight the wild type genotype.


CONCLUSIONS
The frequency of TPMT mutation in a Mediterranean area was low. TPMT genotyping is not a sensitive tool for predicting thiopurine-induced leukopenia.
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Angela
A
Di Salvo
Laboratory of Molecular Genetics, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Carmelo
C
Fabiano
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Vincenza
V
Mannara
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Mariangela
M
Dimarco
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Ambrogio
A
Orlando
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Marco
M
Affronti
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy.
Fabio Salvatore
FS
Macaluso
Di.Bi.M.I.S., Division of Internal Medicine, "Villa Sofia-Cervello" Hospital, Palermo, Italy. Electronic address: mario.cottone@unipa.it.
Mario
M
Cottone
D000328:Adult; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics*; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics*; D007558:Italy; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine
6-Mercaptopurine; Adverse events; Azathioprine; Genetics