Genetic association study of a polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene and schizophrenia among the Chinese population from Taiwan

Abstract

Chandy et al suggested that a novel human neuronal small conductance, calcium-activated potassium channel gene, KCNN3, might be a candidate for schizophrenia.¹ The KCNN3 cDNA sequences contain two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat was found to be highly polymorphic in the Caucasian population from both Europe and USA. Upon comparing the allelic frequency distribution between schizophrenic patients and ethnically matched controls, a significant excess of longer CAG repeats in schizophrenic patients was observed. A similar result was obtained in a recent replication study by Bowen et al,² performed in Caucasians from UK or Eire. These results suggest an association between the longer CAG repeat allele of the KCNN3 gene and schizophrenia susceptibility. To verify if similar results can be observed in the Chinese population, we carried out a case-control study to compare the allelic frequency distribution of the CAG repeat of the KCNN3 gene between 92 Chinese schizophrenic patients and 100 normal controls from Taiwan. No significant difference of the allelic frequency distribution of the second CAG repeats was detected between the two groups (Wilcoxon Rank Sum test, P = 0.664). In addition, no over-representation of CAG repeats longer than the mode (19 repeats) was found in the patients' group (Fisher's exact test, P = 0.739). Thus, our data do not support that the second polymorphic CAG repeat of the KCNN3 gene may have an association with schizophrenia in our population.