Mapping of hKCa3 to chromosome 1q21 and investigation of linkage of CAG repeat polymorphism to schizophrenia

Abstract

CAG trinucleotide polymorphisms in the neuronal small conductance calcium-activated potassium channel gene hKCa3 have been reported to be associated with schizophrenia. Attempts to confirm this finding have met with mixed results. We investigated hKCa3 CAG allele lengths in families from the National Institute of Mental Health (NIMH) Schizophrenia Genetics Initiative, by comparing transmission to discordant siblings and parental transmission to affected offspring. Overall, there was no convincing evidence that hKCa3 CAG lengths differ between schizophrenics and controls. We did, however, observe a trend (P = 0.063) toward over-representation of long (Ն19) CAG repeats in the shorter of the two hKCa3 alleles in schizophrenics. There was no evidence of excessive parental transmission of long CAG repeat alleles to affected offspring. In addition, we re-mapped hKCa3 and found that it resides on chromosome 1q21, in a region which has been linked to familial hemiplegic migraine, but not to schizophrenia. These data provide no significant support for the association of hKCa3 with schizophrenia.

Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study

“…It is noteworthy that the hSKCa3 gene has also been implicated in schizophrenia and bipolar disorders. 6,[14][15][16][17] Although the phenotype of AN and the major psychoses vary considerably, our results may support the hypothesis of common susceptibility genes shared by several psychiatric disorders. Thus, drugs active at the hSKCa3 channel could be considered in the pharmacotherapy of some neuropsychiatric disorders.…”

“…24 The distribution of the alleles in our control population was similar to that previously found in other populations. 6,[15][16][17][18] Comparison of the AN to the control alleles revealed a broad overlap with differences in only one or two CAG repeats in average and modal length. This overlap is not surprising for a common, heterogeneous and probably multifactorial disorder, such as AN.…”

“…11,12 According to a proposed molecular model, SKCa channels may contribute to the genetic susceptibility to schizophrenia and bipolar disorder. 6,13,14 The hSKCa3 (KCNN3) gene is a calcium-activated potassium channel gene 6 localized to chromosome 1q21.3 [14][15][16] It contains a highly polymorphic CAG repeat stretch within the coding region which was found to be associated with schizophrenia, 6,14-17 with longer repeats over-represented in schizophrenic patients compared to normal controls. A similar trend was also demonstrated in patients with bipolar disorder.…”

Polymorphism of CAG motif of SK3 gene is associated with acute oxaliplatin neurotoxicity

“…PCR parameters consisted of 1 cycle at 95°C for 4 min, 35 cycles at 94°c for 1 min, primer annealing at 55°C for 1 min and extension at 72°C for 30 sec. Final PCR extension was performed at 72°C for 2 min [20]. PCR products were analysed on polyacrylamide gel after staining with Ethidium Bromide.…”

“…Polymerase chain reaction (PCR) amplification of the second KCNN3 CAG polymorphism was adapted from the method described by Austin and co-workers [20]. CAGcontaining fragments were amplified from genomic DNA using the primers KCNN3-I-F 5'-CAGCAGCCCCTGGGACCCTCGC and KCNN3-I-R 5'-GGAGTTGGGCGAGCTGAGACAG.…”