Objective: To explore the correlation of polymorphisms of AF4/FMR2 family genes and IL-10 gene with genetic susceptibility to ankylosing spondylitis (AS) and identify the high-risk factors of AS.
Methods: This case-control study was conducted among 207 AS patients and 321 healthy individuals. The tag single nucleotide polymorphisms (SNPs) rs340630, rs241084, rs10865035, rs1698105, and rs1800896 of the AF4/FMR2 family gene and IL-10 gene of the AS patients were genotyped, and the distribution frequencies of the genotypes and alleles were analyzed to explore the relationship between different genetic models and AS and the gene-gene and gene-environment interactions.
Results: Gender ratio, smoking history, drinking history, hypertension, erythrocyte sedimentation rate and C-reactive protein differed significantly between the case group and the control group (P < 0.05). The dominant model and recessive model of AFF1 rs340630, the recessive model of AFF3 rs10865035, and the recessive model of IL-10 rs1800896 were significantly different between the two groups (P=0.031, 0.010, 0.031, and 0.019, respectively). Gene-environment interaction analysis suggested that the interaction model incorporating AFF1 rs340630, AFF2 rs241084, AFF3 rs10865035, AFF4 rs1698105, IL-10 rs1800896, smoking history and drinking history was the best model. The genes related with AF4/FMR2 and IL-10 were enriched in the biological processes of AF4 super extension complex, interleukin family signal transduction, cytokine stimulation and apoptosis. The expression levels of AF4/FMR2 and IL-10 were positively correlated with immune infiltration (r > 0).
Conclusion: The SNPs of AF4/FMR2 and IL-10 genes are associated with the susceptibility to AS, and the interactions of AF4/FMR2 and IL-10 genes with the environmental factors contributes causes AS through immune infiltration.
目的: 探索AF4/FMR2、IL-10基因与强直性脊柱炎(AS)的遗传易感性，发现高危因素及筛选高危人群。
方法: 共纳入207例AS患者和321例对照者。选择AF4/FMR2家族基因以及IL-10基因的标签SNP(rs340630、rs241084、rs10865035、rs1698105、rs1800896)，提取DNA后进行基因分型，分析其基因型、等位基因分布频率，分析不同遗传模型与AS发病的关系，并进行基因-基因、基因-环境的交互作用分析。
结果: AS组和对照组在性别、吸烟史、饮酒史、高血压、血沉、C反应蛋白在病例组和对照组均有差异(P < 0.05)。AFF1 rs340630的显性模型和隐性模型、AFF3 rs10865035的隐性模型、IL-10 rs1800896的隐性模型在AS组与对照组之间有显著性差异(分别为P=0.031、P=0.010、P=0.031、P=0.019)。基因环境交互分析发现AFF1 rs340630，AFF2 rs241084，AFF3 rs10865035，AFF4 rs1698105，IL-10 rs1800896，吸烟史，饮酒史相互作用模型为最佳模型。AF4/FMR2、IL-10相关基因在AFF4超级延伸复合物、白细胞介素家族信号转导、细胞因子刺激、凋亡等过程富集。免疫相关性分析发现AF4/FMR2、IL-10的表达水平与免疫浸润呈正相关(r > 0)。
结论: AF4/FMR2和IL-10基因多态性与AS的易感性相关，AF4/FMR2和IL-10基因与环境交互引起AS，并通过免疫浸润影响AS的进程。
Keywords: AF4/FMR2; IL-10; ankylosing spondylitis; gene polymorphism.