Thiopurine methyltransferase genotype distribution in patients with Crohn's disease

BACKGROUND: Inter-individual response to azathioprine is partly due to inter-individual variation in the thiopurine methyltransferase (TPMT) activity. The TPMT genotype, which reflects the TPMT activity, has previously been studied in healthy Caucasians, with the most common variant allele being TPMT*3A. TPMT genotyping in adult patients with Crohn's disease has never been performed systematically.

AIM: To determine the TPMT genotype distribution in adult patients with Crohn's disease.

METHODS: One hundred and twenty randomly selected Danish patients (64 females and 56 males) with azathioprine-dependent Crohn's disease were included, and a polymerase chain reaction assay was used for TPMT genotyping. The patients were genotyped for the low-level genotype G460-->A and A719-->G transitions.

RESULTS: One hundred and nine patients (90.3%; 95% confidence interval, 84.1-95.3) had a wild-type/ wild-type genotype, whereas 10 patients (8.3%; 95% confidence interval, 4.1-14.8) had one non-functional mutant allele and one patient (0.8%; 95% confidence interval, 0.02-4.6) had two non-functional mutant alleles. Only the TPMT*3A variant allele was found.

CONCLUSIONS: The study showed a TPMT genotype distribution amongst adult Danish patients with Crohn's disease which was similar to the distribution of TPMT variant alleles normally found in healthy Caucasians.