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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 investigate the association between HLA-B * 5801 alleles and severe skin adverse reactions (SCAR) after taking allopurinol in Jiangsu Han population. Methods Subjects were SCAR patients after taking allopurinol (SCAR group, 36 cases), those who took allopurinol after 6 months did not have any adverse reactions (allopurinol group, 50 cases) and healthy volunteers ( Healthy control group, 167 cases). The peripheral venous blood of the subjects was taken and the HLA-B * 5801 alleles were detected by sequence-specific primer-directed polymerase chain reaction and direct sequencing method to analyze the relationship between SCAR and HLA-B * 5801 alleles . Results Among 36 SCAR patients, 22 were male and 14 were female, ranging in age from 21 to 87 years with a median age of 61 years. In the 50 cases of allopurinol control group, there were 42 males and 8 females, aged 49-93 years Age 74 years; gender differences between the two groups were statistically significant (P = 0.02). The daily dose of allopurinol in both groups was 0.1-0.3 g, and the median dose was 0.2 g. In SCAR group, SCAR occurred 5 ~ 47 days after taking allopurinol, including drug hypersensitivity syndrome, severe exudative erythema multiforme (SJS), toxic epidermal necrolysis (TEN) and SJS / TEN Respectively 20,10,3 and 3 cases. The positive rate of HLA-B * 5801 allele was 97.2% (35/36) in SCAR group, 8.0% (4/50) in allopurinol control group, 12.0% (20/167) in healthy control group, * The risk of developing SCAR in 5801-allele positive patients was significantly higher than that of negative ones (odds ratio = 403,95% confidence interval: 43-3761, P = 0.000). The sensitivity and specificity of HLA-B * 5801 allele prediction for allopurinol-induced SCAR were 97.2% and 92.0%, respectively. Conclusion The HLA-B * 5801 allele of Han nationality in Jiangsu Province is strongly correlated with SCAR induced by allopurinol. The screening of HLA-B * 5801 allele before taking allopurinol may reduce the incidence of allopurinol Occurrence of alcohol induced SCAR.