服用抗甲状腺药物Graves病患者血清抗中性粒细胞胞质抗体阳性与HLA-DRB1*09∶01基因多态性相关  

Association of serum antineutrophil cytoplasmic antibody positivity with gene polymorphism of HLA-DRB1*09∶01 in Graves′disease patients receiving antithyroid drugs

作　　者：王佩青 裴剑浩 陈重 陈红梅 蓝颖茹 李忠文 傅晓莹 赖水清 张舒婷 黄萍 余琴 谭少珍 Wang Peiqing;Pei Jianhao;Chen Zhong;Chen Hongmei;Lan Yingru;Li Zhongwen;Fu Xiaoying;Lai Shuiqing;Zhang Shuting;Huang Ping;Yu Qin;Tan Shaozhen(Department of Endocrinology,Guangdong Provincial People′s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510000,China;Department of Endocrinology,Guilin People′s Hospital,Guilin 541000,China)

机构地区：[1]南方医科大学附属广东省人民医院(广东省医学科学院)内分泌科,广州510000 [2]桂林市人民医院内分泌科,541000

出　　处：《中华内分泌代谢杂志》2024年第4期305-311,共7页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的调查血清抗中性粒细胞胞质抗体(antineutrophil cytoplasmic antibody,ANCA)阳性在服用抗甲状腺药物的Graves病人群中的流行情况及相关影响因素,并探讨CD18 rs235326、HLA-DRB1*09∶01、HLA-DQB1*03∶01基因多态性与血清ANCA阳性的相关性。方法收集2020年9月至2021年12月于广东省人民医院就诊的Graves病患者的临床及实验室检查数据进行横断面分析,并从中选取年龄、性别匹配的血清ANCA阳性及阴性患者对上述基因位点进行测序。结果共有173例患者纳入最终分析,其中ANCA阳性患者42例(24.28%),ANCA阴性患者131例(75.72%)。ANCA阳性患者诊断后病程及服药疗程均显著较ANCA阴性组患者长(P<0.001)。在ANCA阳性患者中,71.43%患者均服用过甲巯咪唑及丙硫氧嘧啶,而在ANCA阴性组,66.41%患者仅服用甲巯咪唑(P<0.001)。各有24例ANCA阳性和25例阴性患者进行基因检测,CD18 rs235326基因多态性在2组间无显著差异,HLA-DRB1*09∶01 rs17886918(P=0.005)、rs9269959(P=0.002)和HLA-DQB1*03∶01 rs1130399(P=0.016)、rs1140317(P=0.029)在2组间等位基因分布存在差异。多因素logistic回归分析显示仅HLA-DRB1*09∶01 rs17886918与血清ANCA阳性呈独立相关(P=0.005)。结论Graves病患者服用抗甲状腺药物期间出现ANCA阳性与更长的诊断后病程及服药疗程相关。位于HLA-DRB1*09∶01上的rs17886918基因多态性可能与ANCA阳性相关。Objective To investigate the prevalence and related factors of serum antineutrophil cytoplasmic antibody(ANCA)positivity in Graves′disease patients receiving antithyroid drugs,and to explore the correlation of CD18 rs235326,HLA-DRB1*09∶01,and HLA-DQB1*03∶01 gene polymorphisms with serum ANCA positivity.Methods Clinical and laboratory data of Graves′disease patients who visited Guangdong Provincial People′s Hospital from September 2020 to December 2021 were collected for a cross-sectional analysis.Serum ANCA-positive and ANCA-negative patients matched for age and gender were selected for sequencing of the aforementioned gene loci.Results A total of 173 patients were included in the final analysis.Among them,42 patients(24.28%)were ANCA-positive,while 131 patients(75.72%)were negative.The disease duration and medication treatment duration in ANCA-positive patients was significantly longer compared to ANCA-negative patients(P<0.001).In the ANCA-positive group,71.43%of patients had taken both propylthiouracil and methimazole,while in the ANCA-negative group,66.41%of patients had only taken methimazole(P<0.001).Gene sequencing was performed on 24 ANCA-positive and 25 ANCA-negative patients,respectively.There was no significant difference in CD18 rs235326 gene polymorphism between the two groups,but there were allele distribution differences in rs17886918(P=0.005)and rs9269959(P=0.002)of HLA-DRB1*09∶01,as well as rs1130399(P=0.016)and rs1140317(P=0.029)of HLA-DQB1*03∶01.Multivariate logistic regression analysis showed that only rs17886918 of HLA-DRB1*09∶01 was independently associated with serum ANCA positivity(P=0.005).Conclusion The presence of ANCA positivity during the administration of anti-thyroid drugs in patients with Graves′disease is associated with longer disease duration and medication treatment duration.Gene polymorphism of HLA-DRB1*09∶01 rs17886918 may be associated with ANCA positivity.

关 键 词：抗中性粒细胞胞质抗体 GRAVES病 抗甲状腺药物 基因多态性 人类白细胞抗原基因 

分 类 号：R581.1[医药卫生—内分泌]