Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients.
The functional Val158Met polymorphism (rs4680) located at the gene that codes for the catechol-O-methyltransferase (COMT) has been extensively investigated in schizophrenia although current data are still controversial. Since COMT activity is sexually dimorphic, we carried out two independent studies in homogeneous samples of male and female Spanish schizophrenic patients. In males, we found an association between the homozygous Val genotype and the disorder, which resembled a recessive model (P = 0.022; odds ratio [OR] = 1.67). This Val homozygotes overrepresentation is produced at the expense of the heterozygous individuals decrease, whilst the Met homozygotes showed no differences when compared controls and patients. As a consequence, the heterozygous genotype in this sample had a protective effect (P = 0.03; OR = 0.65) and a strong deviation from Hardy-Weinberg equilibrium in male cases was observed (P = 0.006). In addition, a 2-SNP haplotype analysis (rs4818-Val158Met) confirmed there is an overrepresentation of the different homozygous Val genotypes in the male schizophrenic sample. Regarding females, we did not find any statistically significant association between COMT SNP and schizophrenia. In the light of this we suggest that the Val158Met SNP is involved in risk and protective genotypes for the vulnerability to schizophrenia in Spanish male population.
Hoenicka
Janet
J
Hospital Universitario 12 de Octubre, Servicio de Psiquiatría, Madrid, Spain. jhoenicka@gmail.com
Garrido
Elena
E
Martínez
Isabel
I
Ponce
Guillermo
G
Aragüés
María
M
Rodríguez-Jiménez
Roberto
R
España-Serrano
Laura
L
Alvira-Botero
Ximena
X
Santos
José Luis
JL
Rubio
Gabriel
G
Jiménez-Arriero
Miguel Angel
MA
Palomo
Tomás
T
D001483:Base Sequence; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D012737:Sex Factors; D013030:Spain; D014633:Valine / Q000235:genetics*
D017931:DNA Primers; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine