MIF、MMPs基因交互作用与强直性脊柱炎及免疫相关性研究  

Association of MIF and MMPs gene interaction with ankylosing spondylitis and immunity

作　　者：朱辉[1] 徐永申[1] ZHU Hui;XU Yongshen(The Second Affiliated Hospital of Henan University of Science and Technology,Luoyang 471000,China)

机构地区：[1]河南科技大学第二附属医院,洛阳471000

出　　处：《中国免疫学杂志》2024年第10期2150-2157,共8页Chinese Journal of Immunology

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)。

摘　　要：目的:探索MIF和MMPs家族基因多态性与强直性脊柱炎(AS)的遗传易感性,以及基因-基因、基因-环境交互作用与AS发病的相关性,发现AS的高危因素并筛选AS高危人群。方法:本研究为病例对照研究,共纳入180例AS患者和345例对照者。选择MIF和MMPs家族基因的标签SNP(MIF rs2070767、MIF rs1007888、MMP1 rs498186、MMP2 rs243866、MMP3 rs591058、MMP8 rs11225395),提取DNA后进行基因分型,并进一步分析基因型、等位基因分布频率、遗传模型与AS发病的关系及高危因素。采用广义多因子降维法分析目的基因之间以及基因与环境之间的交互作用与AS的相关性。对MIF、MMPs基因进行功能富集分析及免疫相关性分析。结果:AS组MIF rs1007888、MMP1 rs498186、MMP8 rs11225395最小等位基因的基因型分布频率高于对照组(P<0.05)。MIF rs1007888的GG基因型、MMP1 rs498186的GG基因型、MMP3 rs591058的CT/TT基因型、MMP8 rs11225395的TT基因型与AS的发病风险相关。GMDR基因交互分析发现MMP3 rs591058, MMP8rs11225395相互作用模型为最佳模型。基因环境交互分析发现MIF rs2070767、MIF rs1007888、MMP1 rs498186、MMP2rs243866、MMP3 rs591058、MMP8 rs11225395、吸烟、饮酒、肥胖相互作用模型为最佳模型。MIF、MMPs相关基因在基质金属蛋白酶、巨噬细胞迁移通路及免疫系统调节过程富集。MMPs表达水平与免疫浸润呈正相关。结论:MIF和MMPs基因单核苷酸多态性与AS的易感性相关,且MIF和MMPs基因与环境之间存在交互作用,并可通过多个生物学过程引起AS,并可能通过免疫浸润影响AS的进程。Objective:To explore the genetic susceptibility of MIF and MMPs family gene polymorphisms to ankylosing spon⁃dylitis(AS),as well as the correlation of gene-gene,gene-environment interactions in the pathogenesis of AS,and to find high risk factors of AS and screening of high-risk groups of AS.Methods:A total of 180 AS patients and 345 controls were included in this casecontrol study.Selected the tag SNPs of MIF and MMPs family genes(MIF rs2070767,MIF rs1007888,MMP1 rs498186,MMP2 rs243866,MMP3 rs591058,MMP8 rs11225395),then DNA was extracted and genotyped,and the relationship between genotype,allele distribution frequency,genetic model and the incidence of AS and the risk factors were further analyzed.Generalized multi-fac⁃tor dimensionality reduction method was used to analyze the correlation of the interaction between target genes and between genes and the environment and AS.The functional enrichment analysis and immune correlation analysis of MIF and MMPs were carried out.Re⁃sults:The genotype distribution frequency of the smallest alleles of MIF rs1007888,MMP1 rs498186,MMP8 rs11225395 were higher risks in AS group than in control group(P<0.05).GG genotype of MIFrs1007888,GG genotype of MMP1 rs498186,CT/TT genotype of MMP3 rs591058,and TT genotype of MMP8 rs11225395 were related to the risk of AS.Gene-gene interaction analysis found that MMP3 rs591058 and MMP8 rs11225395 interaction models were the best models.Gene-environment interaction analysis found that MIF rs2070767,MIF rs1007888,MMP1 rs498186,MMP2 rs243866,MMP3 rs591058,MMP8 rs11225395,smoking,drinking,and obesity interaction models were the best models.MIF and MMPs related genes were enriched in matrix metalloproteinases,macro⁃phage migration pathway and immune system regulation.Expression levels of MMPs were positively correlated with immune infiltra⁃tion.Conclusion:The single nucleotide polymorphisms of MIF and MMPs are related to the susceptibility to AS,and there is an inter⁃action between MIF and MMPs genes and the environment,which caus

关 键 词：MIF MMP GMDR 强直性脊柱炎 免疫 

分 类 号：R593.2[医药卫生—内科学]