中国大陆汉族别嘌呤醇重症药疹病人HLA-B*5801等位基因的检测

摘要

Objective:To detect the HLA-B*5801 allele of Han Chinese patients with allopuri-nol-induced severe drug eruption and evaluate the significance of HLA-B*5801 allele as a genetic marker to predict allopurinol-induced severe drug eruption in Han Chinese .Methods:HLA-B*5801 allele genotyping was performed by the polymerase chain reaction-sequence specific primers method in six patients with Stevens-Johnson syndrome ( SJS) or toxic epidermal necrolysis ( TEN) (group A) and four patients with maculopapular eruption (MPE) (group B).In addition, twenty allopurinol-tolerant patients who had used allopurinol for six months without evidence of any drug eruption (group C) and 185 healthy individuals who never used the drug and without severe drug eruption (group D) were recruited as controls.Results:The HLA-B*5801 allele were identified in all six patients (100%) of group A, one patient (25.0%) of group B, two patients (10.0%) of group C and seventeen individuals (9.19%) of group D.Compared with healthy individuals , the frequency of the HLA-B*5801 allele in allopurinol-induced SJS/TEN patients was significantly higher (χ²=45.25, P<0.05).Whileas no statistical significance was found in difference of the frequency of HLA-B*5801 allele both between allopurinol-induced MPE patients and healthy indi-viduals and between allopurinol-tolerant patients and healthy individuals (χ²=1.15,0.01 respec-tively;both P>0.05).Conclusion:In Han Chinese, there is a strong association of HLA-B*5801 allele in patients with allopurinol-induced SJS/TEN, but not in patients with allopurinol-in-duced maculopapular eruption .%目的：检测中国大陆汉族别嘌呤醇重症药疹病人的HLA-B*5801等位基因，并初步评价HLA-B*5801等位基因作为遗传标记预测中国大陆汉族人别嘌呤醇重症药疹的意义。方法：采用 PCR-SSP方法检测6例别嘌呤醇重症药疹（包括Stevens-Johnson综合征和中毒性表皮坏死松解）病人（ A组），4例别嘌呤醇引起的斑丘疹型药疹病人（ B组），20例服用别嘌呤醇超过6个月而没有出现药物过敏现象的病人（ C组）和185例无药物过敏史、且从未服用过别嘌呤醇的健康体检者（ D组）的HLA-B*5801基因型。结果：HLA-B*5801基因阳性例数（频率）分别为：A 组病人6例（100％）， B 组病人1例（25.00％），C组2例（10.00％），D组17例（9.19％）。与健康体检者相比，别嘌呤醇重症药疹病人的HLA-B*5801基因型频率明显较高，其差异有统计学意义（χ²＝45.25，P＜0.05）；而别嘌呤醇引起的斑丘疹型药疹病人及对别嘌呤醇耐受的病人与健康体检者间的差异均无统计学意义（χ²分别为1.15、0.01，P值均＞0.05）。结论：中国大陆汉族人群别嘌呤醇重症药疹与HLA-B*5801等位基因有强烈关联性，而别嘌呤醇引起的斑丘疹型药疹与HLA-B*5801的关联性不大。