摘要
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。
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.
作者
穆杰
徐永申
朱辉
MU Jie;XU Yongshen;ZHU Hui(Second Affiliated Hospital of Henan University of Science and Technology,Luoyang 471000,China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2023年第5期741-748,共8页
Journal of Southern Medical University
基金
河南省科技攻关计划联合共建立项目(LHGJ20200597)
洛阳市科技计划医疗卫生项目(1814004A)。
