Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by severe joint pain. There are conflicting results for the association of Interleukin 4 (IL4) variable number tandem repeats (VNTR; rs8179190) polymorphism with RA. Therefore, we performed a meta-analysis of the available studies to investigate the association of IL4 VNTR polymorphism with RA risk and severity in the overall populations and Asian, Egyptian, European, and Turkish ethnicities by sub-group analyses. Eight studies involving 1993 RA patients and 1732 controls were included in this meta-analysis. We found increased RA risk for the susceptible “R2R2” genotype and “R2” allele under heterozygous, recessive, and allelic models in the Asian populations (p < 0.00001, p < 0.0001, p = 0.001). We observed a significant association between “R2R2” genotype and “R2” allele for RA protection in the Turkish population under heterozygous, recessive, and allelic models (p = 0.01, p = 0.004, p = 0.002). Disease severity-based analysis revealed significant association for “R2R2” genotype and “R2” allele with RA severity under homozygous, heterozygous, recessive, dominant, and allelic models(p = 0.0004, p = 0.03, p = 0.02, p = 0.003, p = 0.01), specifically in Asian populations (p = 0.009, p = 0.02, p = 0.003, p = 0.03, p = 0.01) and under heterozygous, dominant, and allelic genetic models in Egyptian (p = 0.0001, p < 0.0001, p < 0.0001) and European (p = 0.002, p = 0.0007, p = 0.0006) populations. In silico analysis suggested that the susceptible “R2” allele changes the RNA secondary structure to a stable form by changing minimum free energy(ΔG) from − 115.20 to − 136.40 kcal/mol, which might lead to increased stability of IL-4 in RA patients. Overall, the meta-analysis suggests for the involvement of susceptible “R2” allele with RA risk in the Asian populations, RA severity in the overall populations (specifically in Asian, Egyptian, & European populations), and RA protection in the Turkish population.

类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征是严重的关节疼痛。白细胞介素 4 ( IL4 ) 可变数目串联重复序列 (VNTR; rs8179190) 多态性与 RA 之间的关联存在相互矛盾的结果。因此，我们对现有研究进行了荟萃分析，通过亚组分析来调查IL4 VNTR 多态性与总体人群以及亚洲、埃及、欧洲和土耳其种族的 RA 风险和严重程度之间的关联。这项荟萃分析纳入了八项研究，涉及 1993 名 RA 患者和 1732 名对照者。我们发现，在亚洲人群的杂合、隐性和等位基因模型下，易感“R2R2”基因型和“R2”等位基因的 RA 风险增加 ( p  < 0.00001，p < 0.0001，p  = 0.001）。我们在杂合、隐性和等位基因模型下观察到土耳其人群中“R2R2”基因型和“R2”等位基因对 RA 保护的显着相关性（p  = 0.01、p  = 0.004、p  = 0.002）。基于疾病严重程度的分析显示，在纯合、杂合、隐性、显性和等位基因模型下，“R2R2”基因型和“R2”等位基因与 RA 严重程度显着相关（p = 0.0004，p = 0.03，p  = 0.02  ，p  = 0.003  ，p  = 0.01)，特别是在亚洲人群中 ( p  = 0.009, p  = 0.02, p = 0.003，p  = 0.03，p  = 0.01）以及埃及杂合、显性和等位基因遗传模型（p  = 0.0001，p  < 0.0001，p  < 0.0001）和欧洲（p  = 0.002，p  = 0.0007，p = 0.0006) 人口。计算机分析表明，易受影响的“R2”等位基因通过将最小自由能 (ΔG) 从 − 115.20 kcal/mol 更改为 − 136.40 kcal/mol，将 RNA 二级结构改变为稳定形式，这可能导致 RA 中 IL-4 的稳定性增加患者。总体而言，荟萃分析表明，易感“R2”等位基因与亚洲人群中的 RA 风险、总体人群（特别是亚洲、埃及和欧洲人群）中的 RA 严重程度以及土耳其人群中的 RA 保护有关。