CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population.
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...
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doaj-502e2c33adf14b9c89ad5926aee4f3172020-11-25T00:12:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10198610.1371/journal.pone.0101986CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population.Liang SunYunxiao MengYanchen XieHua ZhangZheng ZhangXiaoxia WangBin JiangWei LiYao LiZe YangCytotoxic 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.To investigate the role of CTLA4 variants in the susceptibility to MG and the contribution to subtypes of MG.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.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.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.http://europepmc.org/articles/PMC4086970?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liang Sun Yunxiao Meng Yanchen Xie Hua Zhang Zheng Zhang Xiaoxia Wang Bin Jiang Wei Li Yao Li Ze Yang |
spellingShingle |
Liang Sun Yunxiao Meng Yanchen Xie Hua Zhang Zheng Zhang Xiaoxia Wang Bin Jiang Wei Li Yao Li Ze Yang CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. PLoS ONE |
author_facet |
Liang Sun Yunxiao Meng Yanchen Xie Hua Zhang Zheng Zhang Xiaoxia Wang Bin Jiang Wei Li Yao Li Ze Yang |
author_sort |
Liang Sun |
title |
CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. |
title_short |
CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. |
title_full |
CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. |
title_fullStr |
CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. |
title_full_unstemmed |
CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. |
title_sort |
ctla4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern chinese population. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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.To investigate the role of CTLA4 variants in the susceptibility to MG and the contribution to subtypes of MG.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.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.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. |
url |
http://europepmc.org/articles/PMC4086970?pdf=render |
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