Ha Pham Tran Thu, Tran Quang Binh, Chu Chi Hieu, Nga Do Thi Quynh, Nguyen Hoang Anh, Nguyen Dinh Van, Phung Thanh Huong
Department of Biochemistry, Hanoi University of Pharmacy, Hanoi, 10000, Vietnam.
Department of Nutrition & Non-communicable Diseases, National Institute of Nutrition, Hanoi, 10000, Vietnam.
Pharmacogenomics. 2022 Apr;23(5):303-313. doi: 10.2217/pgs-2021-0156. Epub 2022 Feb 21.
To reveal the association of three class I alleles, including and , and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. A case-control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The and alleles were detected with the nested allele-specific PCR method; the allele was detected with the sequence-specific primer PCR method. There were strong associations between and and allopurinol-induced SCARs. Specific associations were found between and Stevens-Johnson syndrome/toxic epidermal necrolysis and between and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: and estimated glomerular filtration rate <60 ml/min/1.73 m. The specificity, positive predictive value and negative predictive value of testing were higher than the or the multiplex testing, especially in patients with impaired renal function. The results supported pre-treatment testing in Vietnamese patients with declined renal function to prevent SCARs.
揭示包括[具体等位基因1]和[具体等位基因2]在内的三种I类等位基因与越南患者中别嘌醇诱发的严重皮肤不良反应（SCARs）之间的关联。对100例别嘌醇诱发的SCARs患者、183例耐受对照者和810例群体对照者进行了一项病例对照研究。采用巢式等位基因特异性PCR方法检测[具体等位基因1]和[具体等位基因2]；采用序列特异性引物PCR方法检测[具体等位基因3]。[具体等位基因1]和[具体等位基因2]与别嘌醇诱发的SCARs之间存在强关联。在[具体等位基因3]与史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症之间以及[具体等位基因1]与嗜酸性粒细胞增多和全身症状的药物反应之间发现了特定关联，并存在基因剂量效应。多因素回归分析表明有两个显著的独立危险因素：[具体等位基因1]和估计肾小球滤过率<60 ml/min/1.73 m²。[具体等位基因1]检测的特异性、阳性预测值和阴性预测值高于[具体等位基因2]检测或多重检测，尤其是在肾功能受损的患者中。结果支持对肾功能下降的越南患者进行治疗前[具体等位基因1]检测以预防SCARs。
