Whole-genome analysis in Korean patients with autoimmune myasthenia gravis.
OBJECTIVE
The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samples from a Korean Multicenter MG Cohort.


METHODS
To determine new genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an Axiom™ Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patients and 150 neurologically normal controls.


RESULTS
In total, 641 SNPs from five case-control associations showed p-values of less than 10⁻⁵. From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis.


CONCLUSIONS
The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage further studies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.
Department of Neurology, Konyang University College of Medicine, Daejeon, Korea.
Sang-Jun
SJ
Na
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Ji Hyun
JH
Lee
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
So Won
SW
Kim
Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea.
Dae-Seong
DS
Kim
Department of Neurology, Chungnam University Hospital, Daejeon, Korea.
Eun Hee
EH
Shon
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Hyung Jun
HJ
Park
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Ha Young
HY
Shin
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Seung Min
SM
Kim
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Young-Chul
YC
Choi
D015703:Antigens, CD / Q000235:genetics; D044466:Asian People / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009157:Myasthenia Gravis / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D011956:Receptors, Cell Surface; D019837:Ryanodine Receptor Calcium Release Channel; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
CACNA1S; Myasthenia gravis; RYR3; SLAMF1; whole genome-based SNP analysis