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It is well known that polymorphisms of the TPMT gene (coding for thiopourine methyl-transferase), influence response to treatment with azathioprine. Polymorphisms of the ABCB1 gene (coding for p-glycoprotein 170) has been associated with IBD and resistance to treatment but results are conflicting. The aim of this study was to determine the frequencies of TPMT and ABCB1 gene polymorphisms in IBD patients from Crete, a population genetically homogeneous, and how these polymorphisms might influence response to treatment and disease behaviour.A total of 222 IBD patients records were reviewed for intake of azathioprine, possible adverse reactions, response to treatment and need for colectomy. All patients were genotyped for TPMT gene polymorphisms, that have been related to intolerance to azathioprine (G238C, G460A and A719C) as well as ABCB1 gene polymorphisms (G2677T/A and C3435T), using a PCR-RFLP method. The same polymorphisms were also determined in 119 age and sex healthy controls.Allele frequencies of TPMT gene in our study population were found to be in concordance with those reported in other Caucasian populations. 76 IBD patients were identified receiving azathioprine, of whom 16 were discontinued (10 CD, 6 UC) due to adverse reaction. 2 of them were found to carry the G460A and A719G alleles (TPMT 3A genotype) (12.5%). For the ABCB1 gene, G2677T/A allele frequencies were found to be similar to those reported in the literature. There was no association of G2677T/A or C3435T with clinical phenotype, or resistance to treatment. However, 77.3% of 22/222 patients who did not respond to therapy and required surgery, where found to carry both the C3434T and the G2677T mutation.Our study was conducted in a genetically homogenous population in the island of Crete. No correlation of any single SNP was found with either clinical activity or response to treatment. However, most patients who carried both the G2677T and C3435T mutations were refractory to treatment, a finding which implies that resistance to treatment in IBD patients is a more complex issue, which requires the presence of a genetic locus rather than a single SNP.None Declared.