细胞毒性T淋巴细胞相关抗原4基因多态性与抗甲状腺药物所致白细胞减少的相关性  

Relationship between the cytotoxic T lymphocyte-associated antigen 4 gene polymorphisms and the leukopenia caused by antithyroid drugs

作　　者：张卉[1] 阎胜利[1] 王颜刚[1] 史莎莎[1] 韩立慧[1] 

机构地区：[1]青岛大学医学院附属医院内分泌科,山东青岛260003

出　　处：《药物不良反应杂志》2011年第4期213-217,共5页Adverse Drug Reactions Journal

摘　　要：目的：研究中国北方汉族弥漫性毒性甲状腺肿（GD）患者细胞毒性T淋巴细胞相关抗原4（CTLA-4）第1外显子49位点A/G多态性与抗甲状腺药物（ATD）所致白细胞减少的相关性。方法：收集2009年10月至2010年6月到青岛大学医学院附属医院内分泌科就诊的GD患者（GD组）和同期到体检中心查体的健康人群（健康对照组）。GD组分为3个亚组：ATD治疗后白细胞减少组、ATD治疗后白细胞正常组和ATD治疗前白细胞减少组。收集所有研究对象外周非抗凝静脉血血凝块,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性技术测定CTLA-4基因第1外显子49位点基因型,抽取部分样本进行测序,并计算各组的基因型和等位基因频率。结果：GD组211例患者（ATD治疗后白细胞减少组73例,ATD治疗后白细胞正常组86例,GD合并白细胞减少组52例）、健康对照组85例纳入研究。GD组CTLA-4基因第1外显子49位点AA、AG和GG基因型频率分别为2.4%（5例）、38.8%（82例）、58.8%（124例）,A、G等位基因频率分别为21.8%、78.2%;健康对照组AA、AG和GG的基因型频率分别为15.3%（13例）、32.9%（28例）和51.8%（44例）,A和G的等位基因频率分别为31.8%和68.2%;2组的基因型和等位基因频率差异有统计学意义（χ~2=17.74,P=0.000 1;χ~2=6.48,P=0.01）。CTLA-4基因第1外显子49位点基因型和等位基因频率在ATD治疗后白细胞减少组、ATD治疗后白细胞正常组和GD合并白细胞减少组之间差异均无统计学意义（均P〉0.05）。结论：中国北方汉族人群GD发病与CTLA-4基因第1外显子49位点A/G多态性相关,而ATD导致的白细胞减少似乎与其多态性无关。Objective：To study the relationship between the A/G polymorphism at position 49 in exon 1 of cytotoxic T lymphocyte-associated antigen 4（CTLA-4） gene and leukopenia caused by antithyroid drugs（ATD） in the Chinese Han patients with Graves＇ disease （GD） in the north China.Methods：The subjects in this study were patients with GD（the GD group） and the healthy people（the healthy control group） in the medical center for checking the body in the Affiliated Hospital of Qingdao University from September 2009 to June 2010.The GD group comprised 3 subgroups;the post-ATD therapy leucopenia group,the post-ATD therapy normal leucocytes group and the pre-ATD therapy leukopenia group.Clot of non-anticoagulative blood from a peripheral vein in each subject was collected, genomic DNA was extracted,and genotype at position 49 in exon 1 of CTLA-4 gene was detected using polymerase chain reaction-restriction fragment length polymorphism.A part of samples were selected randomly and sequenced.The genotype and allele frequencies were calculated.Results：Two hundred and eleven patients in the GD group（73 patients in the post-ATD therapy leukopenia group,86 patients in the post-ATD therapy normal leucocytes group,and 52 patients in the pre-ATD therapy leukopenia group） and 85 healthy people in the healthy control group were enrolled in this study.In the GD group,the genotype frequencies of AA,AG and GG at position 49 in exon 1 of CTLA-4 gene were 2.4%（5 cases）,38.8%（82 cases）,and 58.8%（124 cases）,respectively;the allele frequencies of A and G were 21.8%and 78.2%,respectively.In the healthy control group,the genotype frequencies of AA,AG and GG were 15.3%（13 cases）,32.9%（28 cases）,and 51.8%（44 cases）;the allele frequencies of A and G were 31.8%and 68.2%, respectively.The differences in the genotype and allele frequencies in the 2 groups were significant（χ~2= 17.74,P =0.000 1;χ~2=6.48, P =0.01）.There were no significant differences in the genotype and allele frequencies at positio

关 键 词：GRAVES病 抗甲状腺药物 白细胞减少 细胞毒性T淋巴细胞相关抗原4基因多态性 

分 类 号：R581.3[医药卫生—内分泌]