rs767455位点多态性与脊柱关节病易感性及血小板、单核细胞和中性粒细胞的相关性分析  

Correlation analysis of rs767455 polymorphisms with susceptibility to spondyloarthritides and counts of platelet,monocyte and neutrophil

作　　者：陈浩杰[1] 高瑛瑛[1] 孔杰 赵婧婧 盛楠 CHEN Hao-Jie;GAO Ying-ying;KONG Jie;ZHAO Jing-jing;SHENG Nan(Department of Rheumatology,Nantong First People's Hospital,Nantong 226001,China;Institute of Experimental and Clinical Immunology,Affiliated Hospital 2 of Nantong University,Nantong 226001,China)

机构地区：[1]南通市第一人民医院风湿免疫科,南通226001 [2]南通大学第二附属医院免疫科研延伸平台,南通226001

出　　处：《现代免疫学》2024年第5期413-421,共9页Current Immunology

基　　金：南通大学临床医学专项项目(2022JZ003);南通市卫生健康委员会项目(QN2023013)。

摘　　要：为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧光侵入探针法检测112例SpA患者和82例健康对照的基因型并做关联分析。统计结果显示rs767455位点与SpA患病无显著性关联,但联合中性粒细胞和HLA-B27比单用HLA-B27对SpA发病预测效果更佳(中性粒细胞+HLA-B27 vs HLA-B27,AUC=0.972 vs AUC=0.944,P=0.009)。此外,以本研究样本临床指标均值或中位数作为平均水平分组比较显示,TC型或CC型SpA患者血小板升高的风险显著高于TT型患者(TC+CC vs TT,OR=3.572,95%CI 1.207~10.574,P=0.022),TC型患者血小板高于平均水平的风险同样高于TT型患者(TC vs TT,OR=3.907,95%CI 1.195~12.778,P=0.024)。相对于携带T等位基因患者,C等位基因携带者血小板数目(C vs T,OR=3.000,95%CI 1.143~7.871,P=0.026)、单核细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)和中性粒细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)高于平均水平的风险显著升高。在不同组织或细胞样本中的连锁分析显示rs767455是TNFRSF1A的剪接数量性状位点(splicing quantitative trait locus,sQTL)。该研究提示,中性粒细胞可能独立于HLA-B27参与SpA的发病,rs767455位点C等位基因可能通过影响可变剪接参与TNFRSF1A的调控,引起SpA患者中性粒细胞水平升高为代表的免疫失衡,对SpA的致病机制研究和临床精准治疗具有一定指导意义。To investigate the correlation of rs767455 polymorphism at tumor necrosis factor receptor superfamily member 1A(TNFRSF1A)with spondyloarthritides(SpA)susceptibility and the clinical indicators,invasive probe based real-time PCR for rs767455 genotyping was employed in 112 SpA patients and 82 healthy controls.The statistical results showed that rs767455 was not significantly associated with the risk of SpA.However,using the combination of neutrophils and HLA-B27 to predict the occurrence of SpA increased the accuracy than HLA-B27 alone(AUC=0.972 of neutrophils+HLA-B27 vs AUC=0.944 of HLA-B27 alone,P=0.009).Correlation analysis using the mean or median of the clinical indicators for stratification showed that the risk of elevated platelet count in SpA patients with TC or CC genotype was significantly higher than that in TT genotype patients(TC+CC vs TT,OR=3.572,95%CI 1.207-10.574,P=0.022).In addition,the risk of elevated platelet counts in TC genotype SpA patients was also higher than that in patients with TT genotype(TC vs TT,OR=3.907,95%CI 1.195-12.778,P=0.024).Moreover,statistical analysis showed that compared to SpA patients carrying the T allele,patients carrying the C allele had a significantly higher probability of higher than average platelet count(C vs T,OR=3.000,95%CI 1.143-7.871,P=0.026),monocyte count(C vs T,OR=2.794,95%CI 1.110-7.033,P=0.029),and neutrophil count(C vs T,OR=2.794,95%CI 1.110-7.033,P=0.029).Linkage analysis showed that rs767455 represented a splicing quantitative trait locus(sQTL)for TNFRSF1A across multiple tissues and cells.Altogether,the results suggest that neutrophils may participate in the pathogenesis of SpA independently of HLA-B27,and rs767455 T allele may play a role in the regulation of TNFRSF1A and lead to immune imbalance represented by elevated neutrophil levels in SpA patients.This study may guide in-depth research on both the pathogenesis and precise treatment of SpA.

关 键 词：脊柱关节病 肿瘤坏死因子受体超家族成员1A 易感性 单核苷酸多态性 

分 类 号：R392.2[医药卫生—免疫学]