别嘌醇致严重皮肤不良反应与江苏汉族人HLA-B~＊5801等位基因的相关性研究  

Correlation between HLA-B~＊5801 allele and allopurinol-induced severe cutaneous adverse reaction in Han ethnic group patients in Jiangsu province

作　　者：高杰[1] 张晶晶[1] 王进[2] 张雯雯[1] 于迪[1] 钱玉兰[1] 郑晓娴[1] 丁肖梁[1] 缪丽燕[1] 

机构地区：[1]苏州大学附属第一医院药学部,215006 [2]苏州大学药学院药理学系

出　　处：《药物不良反应杂志》2013年第5期258-262,共5页Adverse Drug Reactions Journal

基　　金：江苏省医学重点人才项目(RC2011110);江苏省苏州市科技项目(SYS201001)

摘　　要：目的探讨HLA-B~＊5801等位基因与江苏汉族人服用别嘌醇后发生严重皮肤不良反应（SCAR）的相关性。方法受试者为服用别嘌醇后发生SCAR者（SCAR组,36例）、服用别嘌醇6个月后未发生任何不良反应者（别嘌醇对照组,50例）和健康志愿者（健康对照组,167例）。取受试者外周静脉血,采用序列特异性引物引导的聚合酶链反应和直接测序方法检测HLA-B~＊5801等位基因,分析SCAR与HLA-B~＊5801等位基因之间的关系。结果 SCAR组36例中男性22例,女性14例,年龄21~87岁,中位年龄61岁;别嘌醇对照组50例中男性42例,女性8例,年龄49~93岁,中位年龄74岁;2组间性别分布差异有统计学意义（P=0.02）。2组患者别嘌醇日服用剂量均为0.1~0.3 g,中位剂量均为0.2 g。SCAR组患者在服用别嘌醇后5~47 d出现SCAR,其中药物超敏综合征、重症渗出性多形红斑药疹（SJS）、中毒性表皮坏死松解症（TEN）和SJS/TEN者分别为20、10、3和3例。SCAR组HLA-B＊5801等位基因阳性率为97.2%（35/36）,别嘌醇对照组为8.0%（4/50）,健康对照组为12.0%（20/167）,HLA-B＊5801等位基因阳性者发生SCAR的风险显著高于阴性者（比值比=403,95%置信区间：43~3761,P=0.000）。HLA-B＊5801等位基因检测预测别嘌醇致SCAR的敏感性及特异性分别为97.2%和92.0%。结论江苏省汉族人HLA-B~＊5801等位基因与别嘌醇致SCAR具有强相关性,患者服用别嘌醇之前进行HLA-B~＊5801等位基因筛查可能有助于减少别嘌醇所致SCAR的发生。Objective To explore the correlation between HLA-B~＊ 5801 allele and allopurinolinduced severe cutaneous adverse reaction（SCAR） in Han ethnic group patients in Jiangsu province. Methods The patients who developed SCAR after receiving allopurinol were enrolled in SCAR group（36 cases）,the patients without any adverse reaction receiving allopurinol over 6 months were enrolled in allopurinol control group（50 cases） and 167 healthy volunteers were enrolled in healthy control group.The subjects＇ peripheral blood samples were taken to detect the HLA-B~＊ 5801 allele by sequence-specific primer polymerase chain reaction and polymerase chain reaction-sequencing based typing,in order to analyze the correlation between HLA-B~＊5801 allele and allopurinol-induced SCAR.Results There were 36 cases in SCAR group comprised 22 males and 14 females with median age of 61 years（21 to 87 years）.There were 50 cases in allopurinol control group comprised 42 males and 8 females with median age of 74 years（49 to 93 years）.The difference of sexual distribution between 2 groups was statistically significant（P=0.02）. The dose of allopurinol in two groups was 0.1-0.3 g everyday and the median dose was 0.2 daily.The subjects in SCAR group developed SCAR 5 to 47 days after receiving allopurinol.The case number of cases with drug hypersensitivity syndrome,Stevens-Johnson syndrome（SJS）,toxic epidermal necrolysis（TEN） and SJS/TEN were 20,10,3 and 3,respectively.The positive rate of HLA-B ~＊ 5801 allele was 97.2%（35/ 36） in SCAR group,8.0%（4/50） in allopurinol control group,and 12.0%（20/167）in healthy control group.The risk of developing SCAR was significantly higher in subjects with positive HLA-B 5801 allele than those with negative HLA-B ~＊ 5801 allele（OR=403,95%CI：43-3761,P=0.000）.The sensitivity and specificity of the HLA-B~＊ 5801 allele for prediction of allopurinol-induced SCAR were 97.2%and 92.0%,respectively.Conclusions The HLA-B ~＊ 5801 allele in Han ethnic group in Jiangsu

关 键 词：HLA-B~＊5801 别嘌醇 严重皮肤不良反应 

分 类 号：R595.3[医药卫生—内科学]