HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children.
HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children.
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DOI：
10.1038/clpt.2013.55
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发表时间：
2013-07
影响因子：
6.7
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中科院分区：
文献类型：
--
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包括罕见但危及生命的史蒂文斯-约翰逊综合征（SJS）和药物性超敏反应综合征（HSS）在内的超敏反应的发生限制了抗惊厥药卡马西平（CBZ）的使用。HLA-B*15:02和HLA-A*31:01已被确定为亚洲和欧洲患者CBZ超敏反应的预测性遗传标记。为了在北美不同种族背景的儿童患者中复制这些遗传关联，我们研究了来自加拿大各地的42名CBZ超敏儿童和91名CBZ耐受儿童的HLA-A*31:01和HLA-B*15:02。HLA-A*31:01与CBZ-HSS（比值比（OR）： 26.4, p=0.0025）和黄斑丘疹（OR: 8.6, p=0.0037）显著相关，与CBZ-SJS无显著相关性。相反，HLA-B*15:02与CBZ-SJS相关（OR: 38.6, p=0.002），但与HSS和黄斑丘疹无关。这项研究首次证明了HLA-A*31:01与儿童CBZ超敏反应的关联，提供了这种关联的重要复制，并强调了HLA-A*31:01作为各种祖先的预测性生物标志物的重要性。
The occurrence of hypersensitivity reactions including rare but life-threatening Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS) limits the use of the anticonvulsant carbamazepine (CBZ). HLA-B*15:02 and HLA-A*31:01 have been identified as predictive genetic markers for CBZ hypersensitivity in Asian and European patients. To replicate these genetic associations in pediatric patients from North America with a diverse ethnic background, we investigated HLA-A*31:01 and HLA-B*15:02 in 42 children with CBZ hypersensitivity, and 91 CBZ-tolerant children from across Canada. HLA-A*31:01 was significantly associated with CBZ-HSS (odds ratio (OR): 26.4, p=0.0025) and maculopapular exanthems (OR: 8.6, p=0.0037), but not with CBZ-SJS. Conversely, HLA-B*15:02 was associated with CBZ-SJS (OR: 38.6, p=0.002), but not HSS and maculopapular exanthems. This study is the first to demonstrate the association of HLA-A*31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of HLA-A*31:01 as a predictive biomarker across various ancestries.
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影响因子：
168.9
作者：
Marson, Anthony G.;Al-Kharusi, Asya M.;Alwaidh, Muna;Appleton, Richard;Baker, Gus A.;Chadwick, David W.;Cramp, Celia;Cockerell, Oliver C.;Cooper, Paul N.;Doughty, Julie;Eaton, Barbara;Gamble, Carrot;Goulding, Peter J.;Howell, Stephen J. L.;Hughes, Adrian;Jackson, Margaret;Jacoby, Ann;Kellett, Mark;Lawson, Geoffrey R.;Leach, John Paul;Nicolaides, Paola;Roberts, Richard;Shackley, Phil;Shen, Jing;Smith, David F.;Smith, Philip E. M.;Smith, Catrin Tudur;Vanoli, Alessandra;Williamson, Paula R.
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Williamson, Paula R.
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KONISHI, T;NAGANUMA, Y;OKADA, T
通讯作者：
OKADA, T
影响因子：
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作者：
Levi, Natacha;Bastuji-Garin, Sylvie;Maison, Patrick
通讯作者：
Maison, Patrick
影响因子：
2.2
作者：
Kim, Sae-Hoon;Lee, Kyung Wha;Chang, Yoon-Seok
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