title: Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor.
abstract: 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.
authors.affiliation: Department of Pharmacology and Psychiatry, Medical School, University of Extremadura, Badajoz, and Department of Medicine-Neurology, Príncipe de Asturias Hospital, Alcalá de Henares, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: Hortensia
authors.initials: H
authors.lastname: Alonso-Navarro
authors.forename: Félix Javier
authors.initials: FJ
authors.lastname: Jiménez-Jiménez
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Ferrer
authors.forename: Pilar
authors.initials: P
authors.lastname: Vázquez-Torres
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Puertas
authors.forename: José M
authors.initials: JM
authors.lastname: Zurdo
authors.forename: Tomás
authors.initials: T
authors.lastname: López-Alburquerque
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8