de Chaldée M, Laurent C, Thibaut F, Martinez M, Samolyk D, Petit M, Campion D, Mallet J
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Paris, France.
Am J Med Genet. 1999 Oct 15;88(5):452-7. doi: 10.1002/(sici)1096-8628(19991015)88:5<452::aid-ajmg2>3.3.co;2-s.
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.
