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The associations of HLA-DRB1 gene polymorphisms with late-onset myasthenia gravis: a meta-analysis



Late-onset myasthenia gravis (LOMG) is one of the major subgroups of the MG. Intensive evidence suggested that polymorphisms in HLA-DRB1 gene were associated with LOMG risk, but the results remained inconsistent. Therefore, a meta-analysis is conducted to make a more precise evaluation between HLA-DRB1 alleles and LOMG.


The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang and Technology of Chongqing (VIP) Database were searched for eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were applied to assess the association between HLA-DRB1 alleles and LOMG.


A total of 11 studies involving 5513 people were included in our meta-analysis. The results showed that DRB1 07 and 0403 alleles were risk factors for LOMG (1.83 [1.12, 2.98], P = 0.02; 7.05 [2.62, 18.92], P = 0.0001, respectively), while DRB1 0301 and 1301 alleles were identified as protective factors for LOMG (0.44 [0.31, 0.62], P < 0.00001; 0.38 [0.23, 0.62], P = 0.0001, respectively). As for the HLA-DRB1 04 and 14 alleles, our subgroup analysis showed that there were significant associations between these alleles and LOMG in Caucasians (2.21 [1.14, 4.27], P = 0.02; 2.82 [1.29, 6.14], P = 0.009, respectively).


These results confirmed the association of DRB1 alleles (0301, 04, 0403, 07, 1301, and 14) and LOMG, which might provide potential promising biomarkers for prediction of LOMG risk.

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This work was supported by grants from the National Science Foundation of China (Nos. 81460560 and 81960664) and the Applied Basic Research Program of Yunnan Province of China (No. 2017FB134).

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Authors and Affiliations



ML Shen and Y Wang reviewed the topic-related literature and performed the study concept and analysis design. CS Ling performed the data collection, wrote the first draft, analyzed, and interpreted the data. CS Ling, MLShen, Y Wang, WK Cai, XQ Lin, Q Huang, and GH He edited and GH He revised the manuscript. All authors checked interpreted results and approved the final version.

Corresponding author

Correspondence to Gong-Hao He.

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All results and analyses were based on previous ethically-approved studies, thus no further ethical approval and patient consent are required.

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a Forest plots for association between HLA-DRB1 01 allele and LOMG in random model. b Forest plots for association between HLA-DRB1 1501 allele and LOMG in random model (TIF 1494 kb)


Forrest plots for association between HLA-DRB1 alleles and LOMG in six different alleles: a HLA-DRB1 03 allele. b HLA-DRB1 0701 allele. c HLA-DRB1 08 allele. d HLA-DRB1 09 allele. e HLA-DRB1 0901 allele. f HLA-DRB1 10 allele (TIF 3807 kb)


Forrest plots for association between HLA-DRB1 alleles and LOMG in six different alleles: a HLA-DRB1 11 allele. b HLA-DRB1 12 allele. c HLA-DRB1 13 allele. d HLA-DRB1 1302 allele. e HLA-DRB1 15 allele. f HLA-DRB1 16 (TIF 3879 kb)


Forest plots for association between HLA-DRB1 alleles and LOMG according to the ethnicity in four different alleles: a HLA-DRB1 01 allele. b HLA-DRB1 03 allele. c HLA-DRB1 08 allele. d HLA-DRB1 09 allele (TIF 4853 kb)


Forest plots for association between HLA-DRB1 alleles and LOMG according to the ethnicity in three different alleles: a HLA-DRB1 10 allele. b HLA-DRB1 11 allele. c HLA-DRB1 12 allele (TIF 3726 kb)


Forest plots for association between HLA-DRB1 alleles and LOMG according to the ethnicity in three different alleles: a HLA-DRB1 13 allele. b HLA-DRB1 15 allele. c HLA-DRB1 16 allele (TIF 3664 kb)


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Ling, CS., Shen, ML., Wang, Y. et al. The associations of HLA-DRB1 gene polymorphisms with late-onset myasthenia gravis: a meta-analysis. Neurol Sci 41, 1041–1049 (2020).

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  • HLA-DRB1
  • Late-onset myasthenia gravis (LOMG)
  • Polymorphisms
  • meta-analysis