title: Possible association between dysfunction of vitamin D binding protein (GC Globulin) and migraine attacks.
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.
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nagata
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Mishima, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hosomichi
authors.affiliation: Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mitsunaga
authors.affiliation: Division of Genetic Epidemiology Research Support, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mashimo
authors.affiliation: Educational and Research Center, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Educational and Research Center, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Forensic Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Osawa
authors.affiliation: Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Mishima, Japan.
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.affiliation: Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Takizawa
mesh_terms: D000595:Amino Acid Sequence; D002112:Calcifediol / Q000097:blood; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D059472:Exome; D005260:Female; D023061:Gene Order; D056726:Genetic Association Studies; D008040:Genetic Linkage; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008126:Lod Score; D008297:Male; D008881:Migraine Disorders / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D016415:Sequence Alignment; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D014809:Vitamin D-Binding Protein; D015740:Calcitonin Gene-Related Peptide; D002112:Calcifediol