BACKGROUND: Domperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and domperidone targets. AIMS: The aim of this study was to determine if demographic and pharmacogenetic parameters of patients receiving domperidone are associated with response to treatment or side-effects. METHODS: Patients treated with domperidone for gastroparesis provided saliva samples from which DNA was extracted. Fourteen single-nucleotide polymorphisms (SNPs) in seven candidate genes (ABCB1, CYP2D6, DRD2, KCNE1, KCNE2, KCNH2, KCNQ1) were used for genotyping. SNP microarrays were used to assess single-nucleotide polymorphisms in the ADRA1A, ADRA1B, and ADRA1D loci. RESULTS: Forty-eight patients treated with domperidone participated in the study. DNA was successfully obtained from each patient. Age was associated with effectiveness of domperidone (p=0.0088). Genetic polymorphism in KCNH2 was associated with effectiveness of domperidone (p=0.041). The efficacious dose was associated with polymorphism in ABCB1 gene (p=0.0277). The side-effects of domperidone were significantly associated with the SNPs in the promoter region of ADRA1D gene. CONCLUSIONS: Genetic characteristics associated with response to domperidone therapy included polymorphisms in the drug transporter gene ABCB1, the potassium channel KCNH2 gene, and α1D--adrenoceptor ADRA1D gene. Age was associated with a beneficial response to domperidone. If verified in a larger population, this information might be used to help determine which patients with gastroparesis might respond to domperidone and avoid treatment in those who might develop side-effects.
BACKGROUND:Domperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and domperidone targets. AIMS: The aim of this study was to determine if demographic and pharmacogenetic parameters of patients receiving domperidone are associated with response to treatment or side-effects. METHODS:Patients treated with domperidone for gastroparesis provided saliva samples from which DNA was extracted. Fourteen single-nucleotide polymorphisms (SNPs) in seven candidate genes (ABCB1, CYP2D6, DRD2, KCNE1, KCNE2, KCNH2, KCNQ1) were used for genotyping. SNP microarrays were used to assess single-nucleotide polymorphisms in the ADRA1A, ADRA1B, and ADRA1D loci. RESULTS: Forty-eight patients treated with domperidone participated in the study. DNA was successfully obtained from each patient. Age was associated with effectiveness of domperidone (p=0.0088). Genetic polymorphism in KCNH2 was associated with effectiveness of domperidone (p=0.041). The efficacious dose was associated with polymorphism in ABCB1 gene (p=0.0277). The side-effects of domperidone were significantly associated with the SNPs in the promoter region of ADRA1D gene. CONCLUSIONS: Genetic characteristics associated with response to domperidone therapy included polymorphisms in the drug transporter gene ABCB1, the potassium channel KCNH2 gene, and α1D--adrenoceptor ADRA1D gene. Age was associated with a beneficial response to domperidone. If verified in a larger population, this information might be used to help determine which patients with gastroparesis might respond to domperidone and avoid treatment in those who might develop side-effects.
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