Linkage disequilibrium on the COMT gene in French schizophrenics and controls.
Catechol-O-methyltransferase (COMT) catalyzes the degradation of catecholamines and could therefore play a role in the etiology of schizophrenia. Moreover, microdeletions including the COMT locus have been found in schizophrenics presenting typical features of the velo-cardio-facial syndrome. In the present work, five single-strand conformation polymorphisms were detected in exons of the COMT gene. The linkage disequilibria between the polymorphisms were estimated, and the genotypic frequencies were calculated on a sample of 126 to 137 schizophrenics and 136 to 140 controls, depending on the marker. Patients and controls were matched for ethnicity and geographical origin. A trend toward association was found between schizophrenia and (i) genotype 11 of the Pml I polymorphism (p = 0.034; OR = 1.82); (ii) haplotype 1-2 for the Pml I and Bcl I polymorphisms (p = 0.022; OR = 1.75). The Pml I polymorphism is in complete linkage disequilibrium with the common Met-->Val(158) substitution, which affects the activity of the enzyme. This finding suggests a possible minor effect of COMT in a multifactorial threshold model of vulnerability to schizophrenia.
de Chaldée
M
M
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Paris, France.
Laurent
C
C
Thibaut
F
F
Martinez
M
M
Samolyk
D
D
Petit
M
M
Campion
D
D
Mallet
J
J
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D005091:Exons; D005260:Female; D005602:France; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D012559:Schizophrenia / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D002394:Catechol O-Methyltransferase