Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are a great number of polymorphic genes in the human genome. Many of them codify enzymes that metabolizes drugs and xenobiotic agents, including carcinogens. Among the better known of them, there are a number of isozymes of the microsomal oxidative system (CYP3A4, CYP2C9, CYP2C19 y CYP2D6). This article reviews the following issues: a) frequency of presentation of the "poor metabolizer" genotype and/or phenotype for substrates of CYP2C19; b) role of CYP2C19 polymorphism on the metabolism of some drugs (mephenytoine and other antiepileptic drugs, proton pump inhibitors, several antidepressants and anxyolitics, the antimalaria aggent proguanyl, and propranolol, among others, use this metabolic pathway), and c) possible role of CYP2C19 polymorphism in the risk for development of neoplasia and other diseases (systemic lupus erythematosus, psoriasis, hip osteonecrosis, Alzheimer's disease, amyotrophic lateral sclerosis, essential tremor).
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PMID:[The role of CYP2C19 polymorphism in the development of adverse effects to drugs and the risk for diseases]. 1675 80

To identify low-penetrance genes related to sporadic essential tremor (ET) at the CYP2C locus, located in chromosome 10 q23.33. Leukocytary DNA from 200 ET patients and a control group of 300 unrelated healthy individuals with known CYP2C19 genotypes was studied for common CYP2C8 and CYP2C9 allelic variants by using amplification-restriction analyses. Patients with ET showed the following differences compared with healthy subjects: a 1.6-fold reduction in the frequency for CYP2C8*3 (p=0.006), a 1.35-fold reduction of CYP2C9*2 (p=0.05) and a 1.52-fold reduction in the frequency for CYP2C9*3 (p=0.07). The frequency for patients with ET carrying at least one defective allele was 1.33-fold reduced as compared with healthy subjects (p=0.002). In addition, a disruption of the CYP2C8*3/CYP2C9*2 linkage disequilibrium was observed in ET patients, with a 2.1-fold reduction in the percentage for carriers of the haplotype CYP2C8*3 plus CYP2C9*2 in ET patients (p=0.0001). These findings were independent of gender, age, age of onset, or clinical symptoms. These results suggest that alterations at the CYP2C gene locus are associated with the risk for ET.
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PMID:Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor. 1762 38

: We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 due to a genetic deficit and (2) inhibition of CYP2C9 by cotrimoxazole.
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PMID:Severe tremor after cotrimoxazole-induced elevation of venlafaxine serum concentrations in a patient with major depressive disorder. 2366 77