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The human dopamine D4 receptor (DRD4) is of major interest in molccular studies of schizophrenia and personality traits. We examined the association of schizophrenia and polymorphisms in the upstream region of the DRD4 gene (-768G&gt;A in the negative modulator region; -521C&gt;T, -376C &gt;T, and -291C&gt;T in the cell type-specific promoter region; and -616C&gt;G between the two regions) in 208 schizophrenic patients and 210 normal controls. No significant difference in genotype and allele frequencies was observed between the two groups, indicating that these polymorphisms do not make a major contribution to the pathogenesis of schizophrenia. We also studied the association of polymorphisms in the upstream region and a 48-bp repeat polymorphism in exon III of the DRD4 gene with personality traits in 173 Japanese individuals who completed the temperament and character inventory (TCI). The -768G&gt;A polymorphism was significantly associated with reward dependence (P= 0.044), while no significant association was observed between novelty seeking and polymorphisms in the upstream region or the exon III repeat polymorphism of the DRD4 gene.

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits