METAANALYSIS OF DRD3 GENE AND SCHIZOPHRENIA - ETHNIC HETEROGENEITY AND SIGNIFICANT ASSOCIATION IN CAUCASIANS

The involvement of dopamine in the etiology of schizophrenia is sugges ted by a number of neurobiological and pharmacological data, the dopam ine D3 receptor (DRD3) being selectively expressed in brain regions wh ich may be specifically involved in the risk for schizophrenia. The ge ne coding for DRD3 has thus been extensively analyzed. Since the initi al report providing substantial evidence for an association of homozyg osity of either allele of the gene coding for DRD3 (BalI polymorphisms ) with schizophrenia, a flurry of replicating studies has appeared, wh ich have been split into confirmations and nonreplications in North Eu ropean Caucasian, Mediterranean, Asian, American, and African populati ons. The involvement of DRD3 polymorphisms thus remains questionable, particularly as no linkage studies have favored a nonrandom segregatio n of DRD3 alleles and schizophrenia, We performed a metaanalysis from 29 independent samples, from 24 different association studies so far p ublished, allowing the examination of 2,619 schizophrenic patients and 2,517 controls, No significant differences of genotype counts were no ted between patients and controls for the whole sample, considering fr equency of any genotype. Starting from the high variability of the gen otypes in different geographical areas, the impact of ethnic heterogen eity was taken into account. When the studies were reorganized in five groups according to geographical origin of samples, both homozygosity and 1-1 genotype revealed significant heterogeneity (P < 0.05), We sp ecifically found an excess of homozygosity and 1-1 genotype in schizop hrenic patients only in the African and Caucasian groups (P < 0,05), T he present analysis suggests a small but significant effect of DRD3 in the susceptibility to schizophrenia, at least in Caucasians, Am, J, M ed, Genet, (Neuropyschiatr, Genet.) 81:318-322, 1998. (C) 1998 Wiley-L iss, Inc.