No evidence of association from transmission disequilibrium analysis of the hKCa3 gene in bipolar disorder

Abstract

Objective: A recent case-control study has suggested that modest enlargements of a highly polymorphic CAG repeat in exon 1 of the gene encoding potassium channel hKCa3 may be associated with bipolar disorder (BPD). We have examined this hypothesis by genotyping this locus in a family-based association study. Method: One hundred and twenty-eight parent-offspring trios of British Caucasian origin were examined where the proband was diagnosed with the American Psychiatric Association's Diagnostic and Statistical Manual (DSM)-IV BPD I (n = 123) or II (n = 5). An improved assay was used, with redesigned polymerase chain reaction (PCR) primers, permitting quicker and higher resolution genotyping. The resultant genotypes were analysed using the extended transmission/ disequilibrium test (ETDT). Results: The experimental data did not provide evidence for the preferential transmission of large alleles to bipolar cases (χ2 = 11.12, df = 10, p = 0.349). Conclusions: Our data provide no support for the hypothesis that variation at the hKCa3 gene contributes to susceptibility to BPD.