湖南地区携带HLA-B*27꞉04等位基因人群与强直性脊柱炎的易感性具有强相关性  

Association between HLA-B*27:04 and genetic susceptibility to ankylosing spondylitis in Hunan Province

作　　者：陆小芳 万玲 邹凯文 谭亮[3] 朱权 刘荣娇 尹湘丽 宋子璇 位磊艳 向芷青 邹义洲 LU Xiaofang;WAN Ling;ZOU Kevin;TAN Liang;ZHU Quan;LIU Rongjiao;YIN Xiangi;SONG Zixuan;WEI Leiyan;XIANG Zhiqing;ZOU Yizhou(Department of Immunology,School of Basic Medical Sciences,Central South University,Changsha 410013;Xiangya School of Medicine,Central South University,Changsha 410013;Organ Transplant Center,Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]中南大学基础医学院免疫学系,长沙410013 [2]中南大学湘雅医学院,长沙410013 [3]中南大学湘雅二医院器官移植中心,长沙410011

出　　处：《中南大学学报（医学版）》2023年第12期1804-1811,共8页Journal of Central South University ：Medical Science

基　　金：supported by the National Natural Science Foundation of China(82171763).

摘　　要：目的:人类白细胞抗原(human leukocyte antigen,HLA)B27是强直性脊柱炎(ankylosing spondylitis,AS)的易感等位基因,HLA-B27抗原分型是临床诊断AS的重要指标,但目前的分型方法如序列特异引物聚合酶链反应技术(polymerase chain reaction-sequence specific primer,PCR-SSP)等仍存在一定的缺陷。因此,本研究旨在应用高分辨率聚合酶链反应直接测序分型法(polymerase chain reaction-sequence-based typing,PCR-SBT)分析B27亚型与湖南地区强直性脊柱炎易感性的相关性。方法:收集2020年1至12月在湘雅二医院门诊就医的116例疑似AS患者(疑似AS组)和121名健康志愿者(对照组)的外周血,采用PCR-SBT进行HLA-B基因分型。在疑似AS组患者中,23名患者最终被确诊为AS(AS确诊组),其余的93名未能确诊的患者为非AS确诊组。采用PCR-SBT和PCR-SSP检测116例疑似AS患者的HLA-B27分型,并比较2种方法的检测结果。结果:疑似AS组HLA-B27等位基因频率显著高于对照组[11.63%vs 2.48%;P<0.001,优势比(odds ratio,OR)=5.18,95%置信区间(confidence interval,CI)2.097~12.795]。疑似AS组和对照组均检出B*27:04、B*27:05、B*27:06、B*27:07。疑似AS组B*27:04等位基因频率明显高于对照组[9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463~28.282]。疑似AS组和AS确诊组B27阳性率(B27+/+和B27+/-)均显著高于对照组(分别χ^(2)=16.579,P<0.001;χ^(2)=94.582,P<0.001)。在AS确诊组中,21例为HLA-B27携带者,AS确诊组B27阳性率为91.3%。PCR-SBT方法可对HLA-B基因位点进行高分辨分型,其敏感度、特异度、阳性预测值、阴性预测值、准确度均高于PCR-SSP法。结论:应用PCR-SBT检测出HLA-B*27:04与湖南地区AS具有强相关性。PCR-SBT可作为临床AS辅助诊断的优选方案。Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT).Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the nonconfirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared.Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group[9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282].The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+and B27+/−)was significantly higher than that in the control group(χ^(2)=16.579,P<0.001;χ^(2)=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SS

关 键 词：强直性脊柱炎 人类白细胞抗原-B*27:04 遗传易感性 聚合酶链反应直接测序分型法 

分 类 号：R593.23[医药卫生—内科学]