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DRD2 −141C insertion/deletion polymorphism is not associated with schizophrenia: Results of a meta‐analysis

The gene DRD2, which codes for dopamine receptor D2, has been considered a prime candidate for allelic association testing with schizophrenia based on the strong evidence for involvement of this protein in disease pathophysiology. Recent meta‐analyses confirmed a small but reliable association between schizophrenia and the cysteine‐coding allele of the Cys311Ser polymorphism of DRD2. In the present study, we sought to determine if another polymorphism (the −141C insertion/deletion) in the same gene, which has been reported to be associated with schizophrenia in several individual studies, would show a similar pattern of association with the disease in a pooled dataset. The pooled odds ratio for the insertion allele obtained from 10 case‐control studies was 1.1, which was not significant (P = 0.580); however, there was marked heterogeneity among the findings of individual studies, suggesting that some underlying factor influenced the size of their observed effects. Yet, neither ethnicity, the age of the control group, nor the gender composition of the samples reliably influenced effect size. Because linkage disequilibrium patterns between various DRD2 polymorphisms are not yet known, it remains possible that divergent meta‐analytic findings at both commonly examined mutation sites within DRD2 are accurate. Haplotype analysis within this gene would be useful for definitively specifying the role of this gene in the etiology of schizophrenia. © 2004 Wiley‐Liss, Inc.