福建汉族人群服用别嘌醇引起严重皮肤不良反应与HLA-B* 5801关联性

Association of HLA-B* 5801 and allopurinol induced serious cutaneous adverse drug reactions in a Han population from Fujian Province

目的：探讨福建汉族人群服用别嘌醇引起严重皮肤不良反应（SCADRs）与标志基因HLA-B＊5801关联性。方法：收集2012年1月—2013年5月期间福建汉族人群中有服用别嘌醇史住院患者的血液样本,经皮肤科确诊为单一别嘌醇所致SCADRs的患者8例归入别嘌醇重症药疹组,包括剥脱性皮炎（ED）3例,斯-约综合征（SJS）1例,中毒性表皮坏死松解症（TEN）1例,SJS/TEN 3例。期间抽取服用别嘌醇14 d以上未出现皮肤不良反应的患者16例归入耐受组。健康人群318名归入健康对照组。入组患者DNA用聚合酶链-限制性长度多态性法进行标志基因检测,聚合酶链-直接测序法验证检测结果。分析该地区人群服用别嘌醇致SCADRs与HLA-B＊5801的关联性。结果：重症药疹组与耐受组患者在性别、年龄、药物过敏史、肾功能、日剂量及药物暴露天数之间均无统计学差异（P〉0.05）。别嘌醇重症药疹组100.0%（8/8）患者携带HLA-B＊5801基因,别嘌醇耐受组18.8%（3/16）携带（OR=65.57,95%CI：6.7-641.94,敏感度100%,特异度81%,P=0.000 2）,福建健康汉族人群20.4%（65/318）携带（OR=65.79,95%CI：13.71-315.77,P=0.000 1）。结论：福建汉族人群服用别嘌醇所致SCADRs与携带HLA-B＊5801关联性较高,提示该基因检测结果阳性患者应尽量避免服用别嘌醇,以降低发生严重不良反应的风险。

OBJECTIVE To explore the association of marker gene HLA-B＊ 5801 and allopurinol induced serious cutaneous adverse drug reactions（ allopurinol-SCADRs） in a Han population from Fujian Province. METHODS Eight Chinese patients with allopurinol-SCADRs were enrolled,including 3 patients with exfoliative dermatitis（ ED）,1 with Stevens-Johnson syndrome（ SJS）,1 with toxic epidermal necrolysis（ TEN） and 3 with SJS / TEN in severe drug eruption group. Sixteen patients taking allopurinol more than 14 days with no cutaneous adverse reactions were included into tolerance group from 2012 January to 2013 May. A total of 318 healthy persons were enrolled in control group. All samples were from Fujian Han population. DNA was extracted,then HLA-B＊ 5801 was detected by PCR-restriction fragment length polymorphism（ PCR-RFLP）. Detection results were verified by PCR-sequence based typing（PCR-SBT）,then statistically analyzed and discussed. RESULTS No significant difference was found in gender,age,history of drug allergy,renal function,daily dose and drug exposure days among severe drug eruption group or tolerance group（ P〉 0. 05）. Allopurinol-SCADRs patients 100%（8 /8） carried HLA-B＊ 5801,while only 18. 8%（3 /16） patients in the allopurinol-tolerant group（ OR= 65. 57,95% CI：6. 7-641. 94,sensitivity = 100%,specificity = 81%,P = 0. 000 2） and 20. 4% people（ 65 /318） in healthy control group（ OR = 65. 79,95% CI：13. 71-315. 77,P = 0. 000 1） carried the allele. CONCLUSION Strong association of allopurinol-SCADRs with HLA-B＊ 5801 allele is observed in a Han population from Fujian. Patients with positive results should avoid taking allopurinol to reduce risks of serious adverse reactions.