Editing Carbamazepine (section)

=== Pharmacogenetics ===
Serious skin reactions such as [[Stevens–Johnson syndrome]] (SJS) or [[toxic epidermal necrolysis]] (TEN) due to carbamazepine therapy are more common in people with a particular [[human leukocyte antigen]] gene-variant ([[allele]]), [[HLA-B75|HLA-B*1502]].<ref name="carbamazepinelabel"/> [[Odds ratio]]s for the development of SJS or TEN in people who carry the allele can be in the double, triple or even quadruple digits, depending on the population studied.<ref>{{cite journal | vauthors = Kaniwa N, Saito Y | title = Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury | journal = Journal of Human Genetics | volume = 58 | issue = 6 | pages = 317–26 | date = June 2013 | pmid = 23635947 | doi = 10.1038/jhg.2013.37 | doi-access = free }}</ref><ref name="pmid24597466">{{cite journal | vauthors = Amstutz U, Shear NH, Rieder MJ, Hwang S, Fung V, Nakamura H, Connolly MB, Ito S, Carleton BC | title = Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions | journal = Epilepsia | volume = 55 | issue = 4 | pages = 496–506 | date = April 2014 | pmid = 24597466 | doi = 10.1111/epi.12564 | hdl = 2429/63109 | s2cid = 41565230 | hdl-access = free }}</ref> [[HLA-B75|HLA-B*1502]] occurs almost exclusively in people with ancestry across broad areas of Asia, but has a very low or absent frequency in European, Japanese, Korean and African populations.<ref name="carbamazepinelabel"/><ref>{{cite journal | vauthors = Leckband SG, Kelsoe JR, Dunnenberger HM, George AL, Tran E, Berger R, Müller DJ, Whirl-Carrillo M, Caudle KE, Pirmohamed M | title = Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 3 | pages = 324–8 | date = September 2013 | pmid = 23695185 | pmc = 3748365 | doi = 10.1038/clpt.2013.103 }}</ref> However, the HLA-A*31:01 allele has been shown to be a strong predictor of both mild and severe adverse reactions, such as the [[Drug reaction with eosinophilia and systemic symptoms|DRESS]] form of severe cutaneous reactions, to carbamazepine among Japanese, Chinese, Korean, and Europeans.<ref name="pmid24597466"/><ref name="pmid28345177">{{cite journal | vauthors = Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA, Phillips EJ | title = Pharmacogenomics of off-target adverse drug reactions | journal = British Journal of Clinical Pharmacology | volume = 83 | issue = 9 | pages = 1896–1911 | date = September 2017 | pmid = 28345177 | pmc = 5555876 | doi = 10.1111/bcp.13294 }}</ref> It is suggested that carbamazepine acts as a potent antigen that binds to the antigen-presenting area of HLA-B*1502 alike, triggering an everlasting activation signal on immature CD8-T cells, thus resulting in widespread cytotoxic reactions like SJS/TEN.<ref>{{cite journal | vauthors = Jaruthamsophon K, Tipmanee V, Sangiemchoey A, Sukasem C, Limprasert P | title = HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 45553 | date = March 2017 | pmid = 28358139 | pmc = 5372085 | doi = 10.1038/srep45553 | bibcode = 2017NatSR...745553J }}</ref>