FURTHER SUPPORT FOR AN ASSOCIATION BETWEEN A POLYMORPHIC CAG REPEAT IN THE HKCA3 GENE AND SCHIZOPHRENIA

A recent study has suggested that a polymorphism in the hKCa3 potassiu m channel may be associated with raised susceptibility to schizophreni a.(1) Despite its modest statistical significance, the study(1) is int riguing for two reasons. First, hKCa3 contains a polymorphic CAG repea t in its coding sequence, with large repeats more common in schizophre nics compared with controls.(1) This is interesting in view of several repeat expansion detection (RED) studies(2) that have reported an exc ess of large CAG repeats in psychotic probands.(3-7) Second, the hKCa3 gene is a functional candidate gene because studies of antipsychotic and psychotogenic compounds suggest that glutamatergic systems modulat ed by SKCa channels may be important in schizophrenia pathogenesis.(1) In the light of the above, we have tested the hypothesis of an associ ation between schizophrenia and the hKCa3 CAG repeat polymorphism usin g a case control study design. Under the same model of analysis as the earlier study, schizophrenic probands had a higher frequency of allel es with greater than 19 repeats than controls (chi(2) = 2.820, P = 0.0 47, 1-tail). Our data therefore provide modest support for the hypothe sis that polymorphism in the hKCa3 gene may contribute to susceptibili ty to schizophrenia.