title: Polymorphism of transient axonal glycoprotein-1 in chronic inflammatory demyelinating polyneuropathy.
abstract: Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by immune-mediated peripheral demyelination. Although corticosteroid, intravenous immunoglobulin (IVIg), and plasma exchange have been established as the most effective therapeutics, sub-populations of patients show little or no response to either of these therapies. We identified the clinical, electrophysiological, and genetic features related to IVIg responsiveness in CIDP by conducting a multi-center study. Muscle atrophy and decreased compound muscle action potential (CMAP) were pronounced in IVIg non-responders, that is, features suggesting axonal dysfunction in peripheral nerves indicated IVIg unresponsiveness in CIDP. We then performed an association analysis using single nucleotide polymorphisms (SNPs) and haplotype studies between the IVIg responders and non-responders. We assessed SNPs of candidate genes that are particularly related to the function of Ranvier's node, paranode, or juxtaparanode. Two separate SNPs, corresponding to transient axonal glycoprotein-1 (TAG-1) and C-type lectin domain family 10, member A (CLEC10A), showed significant differences between responders and non-responders. Haplotype analysis of a series of expanded SNPs, from TAG-1 or CLEC10A, showed that only TAG-1 included a significant haplotype within one linkage disequilibrium block that accommodates IVIg responsiveness. Diplotype analysis of TAG-1 also supported this observation. In conclusion, SNPs in TAG-1, which is a key molecule for axon-Schwann cell interactions and is distributed at the juxtaparanode, are related to the IVIg responsiveness of CIDP patients.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan. ijama@med.nagoya-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iijima
authors.forename: Haruki
authors.initials: H
authors.lastname: Koike
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D058969:Contactin 2 / Q000235:genetics*; D004351:Drug Resistance; D055106:Genome-Wide Association Study; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000188:drug therapy / Q000235:genetics*
chemical_list: D058969:Contactin 2; D016756:Immunoglobulins, Intravenous