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hSKCa3: a candidate gene for schizophrenia?

B Meissner¹, S Purmann, M Schürmann

¹Institut für Humangenetik, Medizinische Universität zu Lübeck, Germany.

Psychiatric Genetics

|July 21, 1999

Summary

This study investigated the human small-conductance calcium-activated potassium channel gene 3 (hSKCa3) CAG repeat polymorphism in schizophrenia. Our findings do not support the involvement of hSKCa3 in schizophrenia susceptibility.

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Area of Science:

Neuroscience
Genetics
Psychiatry

Background:

Previous case-control studies suggested a link between the hSKCa3 gene's CAG repeat polymorphism and schizophrenia susceptibility.
Larger CAG repeats in hSKCa3 were reportedly overrepresented in patients with schizophrenia.

Purpose of the Study:

To investigate the association between the hSKCa3 CAG repeat polymorphism and schizophrenia.
To examine linkage disequilibrium and perform linkage analysis for hSKCa3 and adjacent markers in multiplex schizophrenia families.

Main Methods:

Extended Transmission/Disequilibrium Test (ETDT) was performed on 12 multiplex schizophrenia families.
Parametric and non-parametric linkage analyses were conducted for hSKCa3 and four microsatellite markers.
Physical localization refinement on chromosome 1q21.3 was achieved using linkage analysis.

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Main Results:

ETDT analysis showed no significant linkage disequilibrium between schizophrenia and hSKCa3 CAG repeat alleles (P = 0.67 allele-wise, P = 0.071 genotype-wise).
No significant results were obtained from parametric or non-parametric linkage analyses for hSKCa3 and the microsatellite markers.
High LOD scores (19.44 and 12.97) were obtained for markers D1S2624 and D1S1600 with hSKCa3, indicating tight linkage at 1q21.3.

Conclusions:

The study does not support the involvement of the hSKCa3 gene in the susceptibility to schizophrenia.
The findings refine the physical mapping of hSKCa3 to chromosome 1q21.3, showing tight linkage with nearby markers.