Association between the catechol-O-methyltransferase Val158Met polymorphism and cocaine dependence.

Lohoff, Falk W; Weller, Andrew E; Bloch, Paul J; Nall, Aleksandra H; Ferraro, Thomas N; Kampman, Kyle M; Pettinati, Helen M; Oslin, David W; Dackis, Charles A; O'Brien, Charles P; Berrettini, Wade H

Lohoff, Falk W; Weller, Andrew E; Bloch, Paul J; Nall, Aleksandra H; Ferraro, Thomas N; Kampman, Kyle M; Pettinati, Helen M; Oslin, David W; Dackis, Charles A; O'Brien, Charles P; Berrettini, Wade H.

Afiliación

Lohoff FW; Department of Psychiatry, Translational Research Laboratories, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. lohoff@mail.med.upenn.edu

Neuropsychopharmacology ; 33(13): 3078-84, 2008 Dec.

Article en En | MEDLINE | ID: mdl-18704099

RESUMEN

Dopaminergic brain systems have been documented to have a major role in drug reward, thus making genes involved in these circuits plausible candidates for susceptibility to substance use disorders. The catechol-O-methyltransferase (COMT) is involved in the degradation of catecholamines and a functional polymorphism (Val158Met) has been suggested to influence enzyme activity. In this study we hypothesize that genetic variation in the COMT gene contributes to increased risk for cocaine dependence. Cocaine-dependent individuals (n=330) and screened unaffected normal controls (n=255) were genotyped for three SNPs in the COMT gene (rs737865, rs4680 (Val158Met), rs165599). All cases and controls were of African descent. Genotype and allele frequencies differed significantly for the Val158Met polymorphism between cases (f(Met)=35%) and controls (f(Met)=27%) (p=0.004; corrected p=0.014; OR 1.44; 95% CI 1.12-1.86). Haplotype analysis showed a significant association for a two-marker haplotype rs737865-Val158Met (p=0.005). Results suggest that variation in COMT increases risk for cocaine dependence. The low enzyme activity 158Met allele or haplotypes containing this variant might have functional effects on dopamine-derived reward processes and cortical functions resulting in increased susceptibility for cocaine dependence. Additional studies are required to elucidate the role of COMT in the pathophysiology of substance use disorders.

Asunto(s)

Química Encefálica/genética; Catecol O-Metiltransferasa/genética; Trastornos Relacionados con Cocaína/enzimología; Trastornos Relacionados con Cocaína/genética; Predisposición Genética a la Enfermedad/genética; Polimorfismo Genético/genética; Adulto; Negro o Afroamericano/genética; Sustitución de Aminoácidos/genética; Química Encefálica/efectos de los fármacos; Estudios de Casos y Controles; Cocaína/farmacología; Trastornos Relacionados con Cocaína/fisiopatología; Análisis Mutacional de ADN; Inhibidores de Captación de Dopamina/farmacología; Femenino; Pruebas Genéticas; Variación Genética/genética; Genotipo; Haplotipos/genética; Humanos; Masculino; Metionina/genética; Persona de Mediana Edad; Valina/genética

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Química Encefálica / Catecol O-Metiltransferasa / Trastornos Relacionados con Cocaína / Predisposición Genética a la Enfermedad Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2008 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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