C. G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Bardoli, Surat, Gujarat, 394 350, India.
Biochem Genet. 2023 Jun;61(3):823-846. doi: 10.1007/s10528-022-10288-3. Epub 2022 Oct 18.
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.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，其特征为严重的关节疼痛。白细胞介素 4（IL4）可变数目串联重复（VNTR；rs8179190）多态性与 RA 的相关性存在争议。因此，我们进行了荟萃分析，以调查在总体人群以及亚洲、埃及、欧洲和土耳其人群中，IL4 VNTR 多态性与 RA 风险和严重程度的相关性，并进行亚组分析。这项荟萃分析纳入了 8 项研究，共涉及 1993 名 RA 患者和 1732 名对照。我们发现，在亚洲人群中，杂合子、隐性和等位基因模型下，易感“R2R2”基因型和“R2”等位基因与 RA 风险增加相关（p<0.00001、p<0.0001、p=0.001）。我们观察到，在土耳其人群中，杂合子、隐性和等位基因模型下，“R2R2”基因型和“R2”等位基因与 RA 保护显著相关（p=0.01、p=0.004、p=0.002）。基于疾病严重程度的分析显示，在亚洲人群中，杂合子、显性和等位基因模型下，“R2R2”基因型和“R2”等位基因与 RA 严重程度显著相关（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），在埃及（p=0.0001、p<0.0001、p<0.0001）和欧洲（p=0.002、p<0.0001、p<0.0006）人群中，杂合子、显性和等位基因模型下也与 RA 严重程度显著相关。基于计算机的分析表明，易感“R2”等位基因通过将最小自由能（ΔG）从-115.20 改变为-136.40 kcal/mol，从而改变 RNA 二级结构，使其变为稳定形式，这可能导致 RA 患者中 IL-4 的稳定性增加。总的来说，这项荟萃分析表明，易感“R2”等位基因与亚洲人群中的 RA 风险、总体人群中的 RA 严重程度（特别是亚洲、埃及和欧洲人群）以及土耳其人群中的 RA 保护有关。
