title: Gene Polymorphisms for Both Auto-antigen and Immune-Modulating Proteins Are Associated with the Susceptibility of Autoimmune Myasthenia Gravis.
abstract: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease against antigens at the neuromuscular junction. Both genetic and environmental factors contribute to the susceptibility of MG. We undertook a case-control study to explore the contribution of genes of the auto-antigen and immune-modulating proteins in the pathogenesis of MG. We enrolled 389 adult MG patients and 487 healthy controls. Eighteen SNPs were selected from genes of cholinergic receptor nicotinic alpha 1 (CHRNA1), autoimmune regulator (AIRE), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), protein tyrosine phosphatase nonreceptor type 22 (PTPN22), and interleukin-10 (IL-10). Rs16862847 and rs2229957 in CHRNA1, rs3761389 in AIRE, and rs733618 in CTLA-4 were significantly associated with MG, with the highest association in SNPs of CHRNA1. Carrier of rs16862847 G allele was found to be an independent risk factor in predicting high-level acetylcholine receptor (AChR) antibodies (P = 0.003, OR = 10.296). Genetic interaction analysis revealed a synergistic effect of CHRNA1 (rs16862847), AIRE (rs3761389), and CTLA-4 (rs733618) in the susceptibility of MG (P < 0.0001, OR = 1.95). These findings highlight the role of auto-antigen gene (CHRNA1) in the autoimmune reactions against AChR and reveal synergistic contribution of genes of both auto-antigen and immune-regulating proteins (AIRE and CTLA-4) in the pathogenesis of MG.
authors: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China. drlhf@163.com.
authors: Hai-Feng
authors: HF
authors: Li
authors: Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Yu
authors: Y
authors: Hong
authors: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors: Xu
authors: X
authors: Zhang
authors: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors: Yanchen
authors: Y
authors: Xie
authors: Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors: Geir Olve
authors: GO
authors: Skeie
authors: Department of Neurology, Peking University First Hospital, Beijing, China.
authors: Hong-Jun
authors: HJ
authors: Hao
authors: Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors: Nils Erik
authors: NE
authors: Gilhus
authors: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors: Bing
authors: B
authors: Liang
authors: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors: Yao-Xian
authors: YX
authors: Yue
authors: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors: Xian-Jun
authors: XJ
authors: Zhang
authors: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors: Xiang
authors: X
authors: Gao
authors: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors: Qi
authors: Q
authors: Wang
authors: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors: Zhe
authors: Z
authors: Gao
authors: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors: Xiao-Jun
authors: XJ
authors: Ding
authors: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors: Min
authors: M
authors: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001324:Autoantigens / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D001324:Autoantigens; D009419:Nerve Tissue Proteins
keywords: Autoimmune regulator (AIRE); Cholinergic receptor nicotinic alpha 1 (CHRNA1); Cytotoxic T lymphocyte-associated protein 4 (CTLA-4); Gene polymorphisms; Myasthenia gravis