title: Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.
abstract: Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions.
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Fangping
authors.initials: F
authors.lastname: Yang
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Sheng-An
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Fu
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Yan
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xinfen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Luo
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
mesh_terms: D000493:Allopurinol / Q000009:adverse effects / Q000276:immunology; D000658:Amoxicillin / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000276:immunology; D000927:Anticonvulsants / Q000009:adverse effects / Q000276:immunology; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers; D002220:Carbamazepine / Q000009:adverse effects / Q000276:immunology; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects / Q000276:immunology; D016022:Case-Control Studies; D002511:Cephalosporins / Q000009:adverse effects; D002681:China / Q000208:ethnology; D016207:Cytokines / Q000276:immunology; D003875:Drug Eruptions / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006074:Gout Suppressants / Q000009:adverse effects / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008704:Methazolamide / Q000009:adverse effects / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012460:Sulfasalazine / Q000009:adverse effects / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D015415:Biomarkers; D002257:Carbonic Anhydrase Inhibitors; D002511:Cephalosporins; D016207:Cytokines; D006074:Gout Suppressants; D015235:HLA-B Antigens; D002220:Carbamazepine; D012460:Sulfasalazine; D000493:Allopurinol; D000658:Amoxicillin; D008704:Methazolamide