-141 C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population

Dopamine has long been hypothesised to be involved in the pathogenesis of s chizophrenia. The dopamine D2 receptor is a major site of action of neurole ptic agents used in the treatment of schizophrenia. Arinami et al. [1997; H uman Mol Genet 6:577-582] have recently sequenced the dopamine receptor 2 ( DRD2) gene in Japanese individuals and identified a novel polymorphism: a s ingle cytosine deletion at position -141 disrupting a BstN1 restriction sit e with a frequency of 0.22 in their control group. They then found a strong association with this polymorphism and schizophrenia (p < 0.001) with an o dds ratio of 0.60 in a Japanese population. We have attempted to verify the ir results by repeating the RFLP analysis on a sample of Scottish schizophr enics and controls. We then combined our data with those from another Briti sh sample recruited using similar procedures. The total combined sample siz e was 439 schizophrenics and 437 controls, We obtained a significant associ ation-p = 0.02 with an odds ratio of 1.41. Schizophrenia is associated with the C insertion in the Japanese, but that association is reversed in Cauca sians, Linkage disequilibrium with a causative polymorphism nearby is the m ost likely explanation for this reverse association. Am. J. Med. Genet, (Ne uropsychiatr, Genet.) 88:407-410, 1999, (C) 1999 Wiley-Liss, Inc.