Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP.
OBJECTIVE
Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by immune-mediated peripheral demyelination. Although corticosteroid, IV immunoglobulin (IVIg) and plasma exchange have been established as the most effective therapeutics, subpopulations of patients show little or no response to either of these therapies. In this study, we examined whether particular genetic factors influence the therapeutic responsiveness of patients with CIDP.


METHODS
One hundred Japanese patients categorized as responders or nonresponders to IVIg therapy participated in our study. We performed an association analysis with single nucleotide polymorphisms (SNPs) and haplotype studies between the IVIg responders and nonresponders.


RESULTS
Two separate SNPs, corresponding to TAG-1 (transient axonal glycoprotein 1) and CLEC10A (C-type lectin domain family 10, member A), showed strong significant differences between responders and nonresponders. Haplotype analysis of a series of expanded SNPs, from TAG-1 or CLEC10A, showed that only TAG-1 included a significant haplotype within 1 linkage disequilibrium block, which accommodates IVIg responsiveness. Diplotype analysis of TAG-1 also supported this observation.


CONCLUSIONS
Transient axonal glycoprotein 1 is a crucial molecule involved in IV immunoglobulin responsiveness in Japanese patients with chronic inflammatory demyelinating polyneuropathy.
Department of Neurology, Nagoya University Graduate School of Medicine, Aichi, Japan.
M
M
Iijima
M
M
Tomita
S
S
Morozumi
Y
Y
Kawagashira
T
T
Nakamura
H
H
Koike
M
M
Katsuno
N
N
Hattori
F
F
Tanaka
M
M
Yamamoto
G
G
Sobue
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D058969:Contactin 2; D005260:Female; D006239:Haplotypes; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007564:Japan / Q000453:epidemiology; D037181:Lectins, C-Type / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D016896:Treatment Outcome
C545222:CLEC10A protein, human; C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D037181:Lectins, C-Type