Association study of CAG repeats in the KCNN3 gene in Israeli patients with major psychosis

Objectives: Several studies reported contradictory findings regarding the association of major psychosis with CAG repeats in the KCNN3 gene. We investigated the contribution of the CAG repeat at the KCNN3 gene, localized to chromosome 1q21.3, to the genetic susceptibility for schizophrenia, schizoaffective and bipolar disorders. Methods: Analysis of the number of CAG repeats and the differences in allele length were performed for Israeli Ashkenazi Jews, non-Ashkenazi Jews, and Arabs diagnosed with major psychosis (n=181) versus matched ethnic controls (n=207). Results: We found no significant difference in the number of CAG repeats between the entire sample of patients and controls. However, an analysis of the differences of allele length revealed a significantly greater number of patients with identical allele length (43.1%) when compared with normal controls (30.4%). Furthermore, an earlier age of non-paranoid schizophrenia onset was found associated with differences in allele sizes. There were no significant differences in the number of CAG repeats and the differences in allele length when subjects were grouped according to gender, ethnic origins of their parents, family history, and diagnostic groups. Conclusions: Our results support the hypothesis that a contribution of the KCNN3 gene to genetic susceptibility to major psychosis and their phenotypic polymorphism may be related to the difference of allele length rather than to the number of CAG repeats.