Mutation in the ITPA gene predicts intolerance to azathioprine.
Inosine triphosphate pyrophosphatase (ITPase) deficiency occurs with polymorphic frequencies in Caucasians and results in the benign accumulation of the inosine nucleotide ITP. In 62 patients treated with azathioprine for inflammatory bowel disease, the ITPA 94C>A deficiency-associated allele was significantly associated with adverse drug reactions (OR 4.2, 95% CI 1.6-11.5, p = 0.0034). Significant associations were found for flu-like symptoms (OR 4.7, 95% CI 1.2-18.1, p = 0.0308), rash (OR 10.3, 95% CI 4.7-62.9, p = 0.0213) and pancreatitis (OR 6.2, CI 1.1-32.6, p = 0.0485). Polymorphism in the ITPA gene thus predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency.
Marinaki
A M
AM
Purine Research Laboratory, Department of Chemical Pathology, Guy's and St Thomas' Hospital, London, UK.
Duley
J A
JA
Arenas
M
M
Ansari
A
A
Sumi
S
S
Lewis
C M
CM
Shobowale-Bakre
M
M
Fairbanks
L D
LD
Sanderson
J
J
D000483:Alleles; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001379:Azathioprine / Q000494:pharmacology*; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*; D012189:Retrospective Studies; D013866:Thioguanine / Q000494:pharmacology; D000097630:Inosine Triphosphatase
D000964:Antimetabolites, Antineoplastic; D001379:Azathioprine; D007166:Immunosuppressive Agents; D011755:Pyrophosphatases; D013866:Thioguanine; D000097630:Inosine Triphosphatase