Pharmacogenomics
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Catechol-O-methyltransferase (COMT) is an enzyme that inactivates biologically-active catechols, including the important neurotransmitters dopamine, noradrenaline and adrenaline. These neurotransmitters are involved in numerous physiological processes, including modulation of pain. ⋯ Increased insight into how genetic variants within the COMT locus affect pain perception will contribute to improved understanding of the mechanisms involved in the development of common human pain disorders and may lead to improved strategies for pain treatment. So far, a remarkable complex relationship between COMT genotypes or haplotypes and pain phenotypes has been revealed.
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We investigated the catechol-O-methyltrasferase (COMT) gene, which is a strong functional and positional candidate gene for schizophrenia and therapeutic response to antipsychotic medication. ⋯ The present study thus indicates that the interacting effects within the COMT gene polymorphisms may influence the disease status and response to risperidone in schizophrenia patients. However, the study needs to be replicated in a larger sample set for confirmation, followed by functional studies.
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Testing a relatively small genomic region with a few hundred SNPs provides limited information. Genome-wide association studies (GWAS) provide an opportunity to overcome the limitation of candidate gene association studies. Here, we report the results of a GWAS for the responses to an NSAID analgesic. ⋯ GWAS for acute clinical pain followed by additional SNP genotyping of a neighboring gene suggests that genetic variations in or near the loci encoding DNA binding proteins play a role in the individual variations in responses to analgesic drugs.
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Multicenter Study
HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Recently, strong associations of HLA-B*1502 and HLA-B*5801 with carbamazepine- and allopurinol-induced severe cutaneous adverse reactions were found in Han Chinese patients, respectively, but ethnic differences in the associations have been reported. The objective of this study is to clarify the involvement of HLA-B*1502 and HLA-B*5801 in Japanese SJS/TEN patients. ⋯ While HLA-B*1502 is unlikely to be associated with carbamazepine-related or aromatic anti-epileptic agent-related SJS/TEN, HLA-B*5801 was significantly associated with allopurinol-related SJS/TEN in Japanese.
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Malignant hyperthermia (MH) is a pharmacogenetic disorder triggered by volatile anesthetics or depolarizing muscle relaxants in predisposed individuals. Exercise or stress-induced MH episodes, in the absence of any obvious pharmacological trigger, have been reported, but these are rare. ⋯ The results of such studies have identified commonalities in functional affects of mutations, and also uncovered unexpected complexities in both the structure and function of the skeletal muscle calcium-release channel. The following review is an attempt to provide a summary of the background to current MH research, and highlight some recent advances in our knowledge of the molecular basis of the phenotypic expression of this disorder.