Genetic Polymorphisms In Guillain-Barre Syndrome: A Field Synopsis And Systematic Meta-Analysis

Objective: Guillain-Barre Syndrome (GBS) is considered to be a complex immune-mediated neuropathy. In the past few years, numerous studies were performed to detect the association between genetic polymorphisms and GBS risk. However, the findings of these studies were controversial. Thus, we conducted this field synopsis and systematic meta-analysis for further evaluating the possible associations between all available genetic polymorphisms and GBS susceptibility.Methods: Relevant studies focusing on the association between all genetic polymorphisms and GBS risk were obtained by a comprehensive literature search. The pooled odds ratios (ORs) as well as 95% confidence intervals (CIs) were used for assessing the strength of association. Subgroup analyses stratified by ethnicity and GBS subtype were further performed. Moreover, sensitive analysis and publication bias were conducted for evaluating the reliability of the results.Results: Among the initial identified 333 articles, 41 articles reporting on 220 genetic polymorphisms were extracted for conducting this systematic review. Then, we performed 95 primary and 94 subgroup meta-analyses for 59 variants with at least three independent studies available. The results showed significant association between four variants (Fc gamma R IIA rs1801274, TNF-alpha rs1800629, HLA DRB1*0401 and HLA DRB1*1301) and GBS susceptibility. In the subgroup analysis, three (TNF-alpha rs1800629, TNF-alpha rs1800630 and TLR4 rs4986790) and two (Fc gamma R IIA rs1801274, HLA DRB1*14) variants showed association with increased GBS risk in Asian and Caucasian population, respectively. Also, TNF-alpha rs1800629 was significant associated with AMAN subtypes of GBS. Furthermore, sensitivity analysis, funnel plots and Egger's test displayed robust results, except for Fc gamma R IIA rs1801274. Additionally, for 161 variants with less than three studies, 17 genetic variants have been found to be significantly related with GBS risk in our systematic review.Interpretation: In our study, we assessed the association between all available genetic polymorphisms and GBS susceptibility. We hope our findings would be helpful for identifying novel genetic biomarkers and potential therapeutic targets for GBS.