Catechol-O-Methyl Transferase Gene Polymorphism and Treatment Response to Clozapine in Refractory Schizophrenia

Lee, Kyu Young; Joo, Eun Jeong; Ahn, Yong Min; Maeng, So Jin; Kim, Yong Sik

Abstract

OBJECTIVE
Disturbances in the biogenic amine pathways have been hypothesized to be the biochemical basis of schizophrenia. Catechol-O-methyl transferase (COMT) gene is an important candidate gene due to its function to metabolically inactivating these amines. We investigated the association between 472 G/A (158val/met) and -287 A/G polymorphisms of COMT gene with response to clozapine treatment in refractory schizophrenia. METHODS: One hundred twenty patients of refractory schizophrenia, who were treated with clozapine longer than six months, were participated in this study. We evaluated treatment response on the basis of the difference of re-hospitalization frequency and hospitalization duration before and after the first clozapine administration day. Genotyping of the 472 G/A and -287 A/G polymorphisms was performed by SNapShot method. RESULTS: In 472 G/A polymor-phism, there were no significant differences of the re-hospitalization frequency and the hospitalization duration between the A (-) group and A (+) group, and also no differences among GG, GA, and AA groups. In -287 A/G polymorphism, there were no significant differences between G (-) group and G (+) group. However, we observed significant differences in the re-hospitalization frequency (F=4.38, p=0.015) and in the hospitalization duration (F=3.90, p=0.024) among three genotype groups. CONCLUSION: We found that the treatment response to clozapine was not associated with COMT 472 G/A polymorphism but was positively associated with -287 A/G polymorphism in refractory schizophrenia. However, This association is not strong enough to conclude the association between -287 A/G polymorphism in COMT gene and clozapine response. Further studies with a large sample are required to verify this positive finding more clearly.