title: Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.
abstract: Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.
authors.affiliation: Departamento de Investigación Neuroquímica, Hospital de Zamudio, Servicio Vasco de Salud, Zamudio, Vizcaya, Spain. mercedes.zumarragaortiz@osakidetza.net
authors.forename: Mercedes
authors.initials: M
authors.lastname: Zumárraga
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dávila
authors.forename: Nieves
authors.initials: N
authors.lastname: Basterreche
authors.forename: Aurora
authors.initials: A
authors.lastname: Arrue
authors.forename: Biotza
authors.initials: B
authors.lastname: Goienetxea
authors.forename: María I
authors.initials: MI
authors.lastname: Zamalloa
authors.forename: Leire
authors.initials: L
authors.lastname: Erkoreka
authors.forename: Sonia
authors.initials: S
authors.lastname: Bustamante
authors.forename: Lucía
authors.initials: L
authors.lastname: Inchausti
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Torres
authors.forename: José
authors.initials: J
authors.lastname: Guimón
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002395:Catecholamines / Q000097:blood*; D005260:Female; D005838:Genotype; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000097:blood / Q000201:enzymology / Q000235:genetics*
chemical_list: D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D006719:Homovanillic Acid