| Hung SI |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=1 ------>paper_class2=1 ------>vol=16 ------>confirm_bywho=chlin ------>insert_bywho=cmbwrlee ------>Jurnal_Rank=None ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=306 ------>medlineContent= ------>unit=E0200 ------>insert_date=20060505 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=444 ------>journal_name=Pharmacogenet Genomics ------>paper_name=Genetic susceptibility to carbamazepine-induced cutaneous adverse reactions ------>confirm_date=20060512 ------>tch_id=082004 ------>pmid=16538176 ------>page1=297 ------>fullAbstract=The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific. ------>tmu_sno=None ------>sno=13778 ------>authors2=Chung WH ------>authors3=Jee SH ------>authors4=Chen WC ------>authors5=Chang YT ------>authors6=Lee WR, HuSL, Wu MT, Chen GS, Wong TW, Hsiao PF ------>authors6_c= ------>authors=Hung SI ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=4 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=4 |