Possible association between dysfunction of vitamin D binding protein (GC Globulin) and migraine attacks

Eiichiro Nagata, Natsuko Fujii, Kazuyoshi Hosomichi, Shigeki Mitsunaga, Yoichi Suzuki, Yoichi Mashimo, Hideo Tsukamoto, Tadayuki Satoh, Motoki Osawa, Ituro Inoue, Akira Hata, Shunya Takizawa

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Abstract To identify the genetic causality of migraine and acute, severe melalgia, we performed a linkage analysis and exome sequencing in a family with four affected individuals. We identified a variant (R21L) in exon 2 of the GC globulin gene, which is involved in the transportation of vitamin D metabolites and acts as a chemotaxic factor; this variant was co-segregated within the family. To investigate the relationship between GC globulin and melalgia, we investigated the cytokine levels in serum samples from the patients and control subjects using a cytokine antibody array. GC globulin can bind to both MCP-1 and RANTES in human serum but has a higher affinity to MCP-1. In cell culture systems, MCP-1 was able to bind to overexpressed wild-type GC globulin but not to the GC globulin variant, and the GC globulin binding affinity to MCP-1 was significantly lower in sera from the patients than in sera from control subjects. A higher concentration of MCP-1 was also observed in sera from the patients. Thus, the dysfunctional GC globulin affected cytokine release, especially the release of MCP-1, and MCP-1 might play important roles in melalgia and migraine.

Original languageEnglish
Article numbere105319
JournalPloS one
Issue number8
Publication statusPublished - 2014 Aug 22

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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