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Published on: October 10, 2017
CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder
Joel Jakobsson1, Erik Pålsson2, Carl Sellgren2
1Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden joel.jakobsson@neuro.gu.se.
Abstract:
Several genome-wide association studies and case-control studies have associated the single nucleotide polymorphism (SNP) rs1006737, situated in CACNA1C encoding the alpha 1C subunit of the L-type voltage-gated calcium channel, with bipolar disorder and other psychiatric disorders. However, the causal pathway linking genetic variants in CACNA1C with increased risk for developing brain disorders remains unclear. Here, we explored the association between the rs1006737 SNP and cerebrospinal fluid (CSF) markers. We found a significant association between the risk allele in rs1006737 and a decreased CSF hyperphosphorylated tau/total tau ratio in patients with bipolar disorder, thus linking variation in the CACNA1C gene to a neurochemical marker of neuroaxonal plasticity in those with this disorder.
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