[COMT Val158Met polymorphism and schizophrenia in a series of Spanish patients].
OBJECTIVE
Catecol-O-methyl transferase (COMT) enzyme plays a significant role in the regulation of the dopaminergic system in the prefrontal cortex. Several studies have assessed the association between modifications of the COMT activity and schizophrenia, but without consistent results. COMT gene contains a single nucleotide functional polymorphism which produces the change of a valine for a methionine at position 158. The effect of this aminoacid change is a modification of COMT enzymatic activity: valine-COMT displays a significantly higher capacity of postsynaptic dopamine degradation than methionine-COMT. The objective of this study is to carry out a genetic association study of the functional polymorphism Val158Met in a sample of Spanish schizophrenic patients and healthy controls.


METHODS
This is a case-control study made up of 177 patients and 141 healthy controls. All patients -115 males and 62 females, with ages between 27 and 49 years; mean (standard deviation) of 38 (10.7) years- were being treated in the outpatient Psychiatric Clinic of the Hospital Universitario 12 de Octubre, and fulfilled the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria for schizophrenia (n = 162) or schizoaffective disorder (n = 15). Control subjects -92 males and 49 females, with ages between 26 and 47 years; mean of 36 (9.4) years- were free from medical and psychiatric disorders. Genotype identification was done by means of human genetic molecular techniques coupled to ADN polymerase chain reaction and single strand conformational polymorphism (SSCP) of the COMT Val158Met polymorphism.


RESULTS
No statisticaly significant differences were found in the allele frequencies for this polymorphism between patient and control samples. Nevertheless, in genotype analysis and when a model of recessive inheritance (Val/Val vs Val/Met and Met/Met) was assumed, a possible tendency towards statistical significance was observed. Our results do not allow to confirm the possible COMT gene variants contribution to schizophrenia etiopathogenesis, but they offer some evidence which would point to its implication in some patients subgroups.


CONCLUSIONS
With the results obtained in this study a possible contribution of the COMT gene in schizophrenia etiopathogenesis cannot be ruled out. The issue of the possible effect of the COMT Val158Met polymorphism in schizophrenia would remain to be open and calls for the need to replicate this kind of studies in greater samples that will allow stratificate analysis by patients subgroups.
Díez-Martín
Justo
J
Servicio de Psiquiatría, Hospital Universitario 12 de Octubre, Madrid, España. justodiez@ya.com
Hoenicka
Janet
J
Martínez
Isabel
I
Aragüés
María
M
Rodríguez-Jiménez
Roberto
R
Jiménez-Arriero
Miguel Angel
MA
Ponce
Guillermo
G
Rubio
Gabriel
G
Palomo
Tomás
T
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
D003062:Codon; D002394:Catechol O-Methyltransferase; D004298:Dopamine