PMID- 34122097 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210615 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - HLA Risk Alleles in Aromatic Antiepileptic Drug-Induced Maculopapular Exanthema. PG - 671572 LID - 10.3389/fphar.2021.671572 [doi] LID - 671572 AB - To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE (p = 0.002, p (c) = 0.04). HLA-B*38:02 was associated with CBZ-MPE (p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE (p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE. CI - Copyright (c) 2021 Shi, Wang, Min, Bian, Mao, Mao, Qin, Li, Ou, Hou, Zou, Guan, He, Chen, Li, Wang, Deng, Liu, Shen, Liu, Yi, Zhou, Zhou, Kwan and Liao. FAU - Shi, Yi-Wu AU - Shi YW AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Wang, Jie AU - Wang J AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Min, Fu-Li AU - Min FL AD - Department of Neurology, Guangzhou First People's Hospital, Guangzhou, China. FAU - Bian, Wen-Jun AU - Bian WJ AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Mao, Bi-Jun AU - Mao BJ AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Mao, Yong AU - Mao Y AD - BGI-Shenzhen, Shenzhen, China. FAU - Qin, Bing AU - Qin B AD - Epilepsy Center and Department of Neurosurgery, The First Affiliated Hospital, Jinan University, Guangzhou, China. FAU - Li, Bing-Mei AU - Li BM AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Ou, Yang-Mei AU - Ou YM AD - Department of Neurology, Guangdong 999 Brain Hospital, Guangzhou, China. FAU - Hou, Yun-Qi AU - Hou YQ AD - The First People's Hospital of Shunde, Foshan, China. FAU - Zou, Xin AU - Zou X AD - The Third People's Hospital of Mianyang, Mianyang, China. FAU - Guan, Bao-Zhu AU - Guan BZ AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - He, Na AU - He N AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Chen, Yong-Jun AU - Chen YJ AD - Department of Neurology, Nanhua Hospital Affiliated to South China University, Hengyang, China. FAU - Li, Xue-Lian AU - Li XL AD - Department of Neurology, The Affiliated Yuebei People's Hospital of Shantou University Medical College, Shaoguan, China. FAU - Wang, Juan AU - Wang J AD - The Affiliated Hospital of Xiangnan University, Chenzhou, China. FAU - Deng, Wei-Yi AU - Deng WY AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Liu, Han-Kui AU - Liu HK AD - BGI-Shenzhen, Shenzhen, China. FAU - Shen, Nan-Xiang AU - Shen NX AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Liu, Xiao-Rong AU - Liu XR AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Yi, Yong-Hong AU - Yi YH AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. FAU - Zhou, Lie-Min AU - Zhou LM AD - Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-Set University, Guangzhou, China. FAU - Zhou, Dong AU - Zhou D AD - West China Hospital, Sichuan University, Chengdu, China. FAU - Kwan, Patrick AU - Kwan P AD - Department of Neuroscience, Central Clinical School, Monash University, Alfred Hospital, Melbourne, VIC, Australia. FAU - Liao, Wei-Ping AU - Liao WP AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. LA - eng PT - Journal Article DEP - 20210526 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8187898 OTO - NOTNLM OT - antiepileptic drugs OT - human leukocyte antigen OT - maculopapular exanthema OT - oxcarbazepine OT - risk factor COIS- Authors YM and HL were employed by the company BGI-Shenzhen. The remaining authors declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/15 06:00 MHDA- 2021/06/15 06:01 PMCR- 2021/05/26 CRDT- 2021/06/14 09:35 PHST- 2021/02/26 00:00 [received] PHST- 2021/05/07 00:00 [accepted] PHST- 2021/06/14 09:35 [entrez] PHST- 2021/06/15 06:00 [pubmed] PHST- 2021/06/15 06:01 [medline] PHST- 2021/05/26 00:00 [pmc-release] AID - 671572 [pii] AID - 10.3389/fphar.2021.671572 [doi] PST - epublish SO - Front Pharmacol. 2021 May 26;12:671572. doi: 10.3389/fphar.2021.671572. eCollection 2021.