Koomdee Napatrupron, Pratoomwun Jirawat, Jantararoungtong Thawinee, Theeramoke Voralaksana, Tassaneeyakul Wichittra, Klaewsongkram Jettanong, Rerkpattanapipat Ticha, Santon Siwalee, Puangpetch Apichaya, Intusoma Utcharee, Tempark Therdpong, Deesudchit Tayard, Satapornpong Patompong, Visudtibhan Anannit, Sukasem Chonlaphat
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Front Pharmacol. 2017 Nov 29;8:879. doi: 10.3389/fphar.2017.00879. eCollection 2017.
Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR). This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen () alleles in Thai patients. Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens-Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. and genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes. The proportion of and allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60-38.25; = 0.013, and OR: 4.89; 95% CI: 1.28-18.67; = 0.014]. In addition, subjects with , , and were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83-37.41; = 0.005, OR: 7.33; 95% CI: 1.63-33.02; = 0.005; and OR: 10.29; 95% CI: 1.45-72.81; = 0.029). In contrast to the LTG-induced MPE group, there were no significant differences between alleles and LTG-induced SCAR group. and were associated with LTG-induced CADR in Thai patients. We also identified an association between , , and and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed.
拉莫三嗪（LTG）常用于治疗癫痫和双相情感障碍。它是皮肤药物不良反应（CADR）的常见原因之一。LTG诱导的CADR的临床症状从斑丘疹性皮疹（MPE）到严重皮肤不良反应（SCAR）不等。本研究旨在确定泰国患者中LTG诱导的CADR与人类白细胞抗原（）等位基因的关联。该研究纳入了15例LTG诱导的CADR患者[10例MPE；4例史蒂文斯-约翰逊综合征；1例伴有嗜酸性粒细胞增多和全身症状的药物反应]和50例对LTG耐受的对照。使用聚合酶链反应-序列特异性寡核苷酸探针进行和基因分型。LTG诱导的CADR组中，和等位基因携带者的比例显著高于耐受对照组[优势比（OR）：7.83；95%置信区间（CI）：1.60 - 38.25；= 0.013，OR：4.89；95% CI：1.28 - 18.67；= 故0.014]。此外，LTG诱导的MPE组中携带、和的受试者显著高于耐受对照组（OR：8.27；95% CI：1.83 - 37.41；= 0.005，OR：7.33；95% CI：1.63 - 33.02；= 0.005；OR：提示10.29；95% CI：1.45 - 72.81；= 0.029）。与LTG诱导的MPE组相反而言，等位基因与LTG诱导的SCAR组之间无显著差异。和与泰国患者中LTG诱导的CADR相关。我们还在该人群中确定了、和与LTG诱导的MPE之间的关联。这些结果表明，这些等位基因可能是泰国患者在LTG治疗前预防CADR的有用筛查标志物，但需要更大样本量的进一步重复研究。
