title: CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population.
abstract: BACKGROUND
  Cytotoxic T lymphocyte-associated antigen-4 (CTLA4), a critical negative regulator of the T-cell response, has been considered a candidate for many autoimmune diseases. Evidence from Caucasians supported a genetic predisposition of CTLA4 to myasthenia gravis (MG), but the contribution in East Asians has not been established.
  
  
  OBJECTIVE
  To investigate the role of CTLA4 variants in the susceptibility to MG and the contribution to subtypes of MG.
  
  
  METHODS
  Six autoimmune disease-related risk alleles of CTLA4 (rs1863800, rs733618, rs4553808, rs5742909, rs231775, and rs3087243) were investigated for MG in northern Chinese. 168 patients with MG (mean age 37.1±20.5 years, 64 men and 104 women) and 233 healthy controls (mean age 53.3±8.7 years, 96 men and 137 women) were screened, and the contribution of CTLA4 to the general risk of MG and each subgroup was explored.
  
  
  RESULTS
  rs1863800*C, rs733618*C, and rs231775*G were significantly associated with the whole cohort of patients with MG after permutation correction for multiple-testing adjustment (P = 0.027, 0.001, and 0.032, respectively). A risk haplotype (CCACG) [odds ratio (OR) = 1.535, range = 1.150-2.059, P = 0.004)] was also identified. The stratified subtype analysis indicated that the positive contribution was possibly derived from early onset MG (EOMG), seropositive MG (SPMG), female patients, and MG without thymoma. No association was observed in juvenile MG/LOMG, and MG coupled with thymoma.
  
  
  CONCLUSIONS
  A predisposing effect of rs1863800*C, rs733618*C, and rs231775*G of CTLA4 gene to general risk of MG in Chinese was demonstrated for the first time, which was likely derived from EOMG, SPMG, MG without thymoma and the female patients.
authors.affiliation: The key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Tsinghua University, Beijing, China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yanchen
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurology, Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Public Health, Ningxia Medical University, Yinchuan, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: The key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics*; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human