Purpose: To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP- glucuronosyltransferase 1A9 genotypes UGT1A91b and UGT1A93a, which were previously identified in individual cases of COMT inhibitor-induced toxicity. Methods: The study included 52 Parkinson's disease (PD) patients on COMT inhibitors without evidence of adverse reactions and 11 PD patients who had been withdrawn from COMT inhibitors due to adverse reactions. UGT1A91b was identified by direct sequencing of the PCR amplification of the gene and UGT1A93a was assayed by real-time PCR. Results: The frequency of the3a/3a and1/3a genotype variants was 45.5 % in subjects with adverse reactions and 21.1 % in subjects without adverse reactions [overall UGT1A93a allele frequency 27.3 vs. 11.5 %, P=0.087; odds ratio (OR) 2.87, 95 % confidence interval (CI) 0.94-8.77]. The frequency of genotype combinations leading to low glucuronosyltransferase activity (3a/3a irrespective of1b or1/3a and1/1b) was 5.8 % in subjects without adverse reactions and 36.4 % in subjects with adverse reactions (P=0.014; OR 9.33, 95 % CI 1.71-50.78). Conclusions: In PD patients UDP-glucuronosyltransferase 1A9 genotypes are associated with adverse reactions to COMT inhibitors, leading to treatment withdrawal. UDP-glucuronosyltransferase 1A9 genotyping may be a screening and/or diagnostic test to assist individualized treatments with COMT inhibitors. © 2012 Springer-Verlag.
Association of UDP-glucuronosyltransferase 1A9 polymorphisms with adverse reactions to catechol-O-methyltransferase inhibitors in Parkinson's disease patients
Blandini F.;
2012-01-01
Abstract
Purpose: To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP- glucuronosyltransferase 1A9 genotypes UGT1A91b and UGT1A93a, which were previously identified in individual cases of COMT inhibitor-induced toxicity. Methods: The study included 52 Parkinson's disease (PD) patients on COMT inhibitors without evidence of adverse reactions and 11 PD patients who had been withdrawn from COMT inhibitors due to adverse reactions. UGT1A91b was identified by direct sequencing of the PCR amplification of the gene and UGT1A93a was assayed by real-time PCR. Results: The frequency of the3a/3a and1/3a genotype variants was 45.5 % in subjects with adverse reactions and 21.1 % in subjects without adverse reactions [overall UGT1A93a allele frequency 27.3 vs. 11.5 %, P=0.087; odds ratio (OR) 2.87, 95 % confidence interval (CI) 0.94-8.77]. The frequency of genotype combinations leading to low glucuronosyltransferase activity (3a/3a irrespective of1b or1/3a and1/1b) was 5.8 % in subjects without adverse reactions and 36.4 % in subjects with adverse reactions (P=0.014; OR 9.33, 95 % CI 1.71-50.78). Conclusions: In PD patients UDP-glucuronosyltransferase 1A9 genotypes are associated with adverse reactions to COMT inhibitors, leading to treatment withdrawal. UDP-glucuronosyltransferase 1A9 genotyping may be a screening and/or diagnostic test to assist individualized treatments with COMT inhibitors. © 2012 Springer-Verlag.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
