Research Article: Meta-analyses of IL1A polymorphisms and the risk of several autoimmune diseases published in databases

Date Published: June 7, 2018

Publisher: Public Library of Science

Author(s): Hang Su, Na Rei, Lei Zhang, Jiaxiang Cheng, Sunil K. Ahuja.


Based on published data, we aimed to quantitatively elucidate the possible genetic influence of rs17561 G/T and rs1800587 C/T polymorphisms of the IL1A (interleukin 1 alpha) gene in the susceptibility to several autoimmune diseases.

A series of meta-analyses were carried out. After database searching, we utilized our inclusion/exclusion criteria to screen and include the eligible studies. Passociation (P value of association test), Bonferroni-corrected Passociation value; false discovery rate (FDR)-corrected Passociation, ORs (odd ratios), and 95% CI (confidence interval) were generated to assess the magnitudes of genetic relationships.

A total of 35 eligible articles were included. Pooled analysis data of both rs17561 G/T and rs1800587 C/T in the overall population indicated a negative association between cases of autoimmune diseases and negative controls (all Passociation>0.05, Bonferroni-corrected Passociation>0.05, FDR-corrected Passociation>0.05). Similar results were found in most subgroup analyses (all Passociation>0.05, Bonferroni-corrected Passociation>0.05, FDR-corrected Passociation>0.05), apart from the rs1800587 in the Graves’ disease subgroup, which showed an increased risk in some cases, compared with controls, under the models of allele T vs. C, carrier T vs. C, CT+TT vs. CC, and CT vs. CC (all Passociation<0.05, Bonferroni-corrected Passociation<0.05, FDR-corrected Passociation>0.05, OR>1).

Based on the available data, C/T genotype of the rs1800587 polymorphism within IL1A gene may be associated with an increased Graves’ disease risk. We did not see evidence regarding a positive role for rs1800587 or rs17561 in the risk of other autoimmune diseases, such as systemic sclerosis or rheumatoid arthritis. These conclusions still merit further data support and molecular exploration.

Partial Text

Human autoimmune diseases are a group of pathologies that cause clinical damage or destruction of body tissue due to an immune response to its own antigens [1, 2]. There are many types of autoimmune diseases, such as SSC (systemic sclerosis), JIA (juvenile idiopathic arthritis), BD (Behcet’s disease), RA (rheumatoid arthritis), MS (multiple sclerosis), GD (Graves’ disease), SLE (systemic lupus erythematosus), and TID (type 1 diabetes) [1, 2]. A few cytokine genes have been reported to be linked to the autoimmune disease [2–4].

The meta-analysis was conducted per the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines [21]. S1 File illustrates the meta-analysis on genetic association studies checklist, and S2 File shows the PRISMA 2009 checklist.

Previously, the rs1800587 C/T SNP of IL1A gene was reported to not be linked to the risk or severity of systemic lupus erythematosus in a Spanish population [12], juvenile idiopathic arthritis in an Iranian population [15], and juvenile idiopathic arthritis in the UK [13]. IL1A rs17561 SNP was not associated with rheumatoid arthritis susceptibility in a Mexican population [14]. However, the IL1A rs1800587 and rs17561 SNPs were also reported to be associated with the risk of systemic sclerosis in a Japanese population [8]. The rs1800587 C/T SNP of IL1A gene has been related to susceptibility to systemic sclerosis in a Slovak Caucasian population [9], Graves’ ophthalmopathy in an Iranian population [10], and Graves’ disease in a Tunisian population [11]. Therefore, we first comprehensively explored the association between IL1A rs17561 and rs1800587 SNPs and the risk of overall autoimmune diseases using meta-analysis and subgroup analyses by characteristics of ethnicity, disease type and source of control.




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