HLA-B~* 1502表达与AEDs致敏相关性的临床研究
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摘要
目的探讨HLA-B~*1502表达与癫痫药物芳香族(aromatic antiepileptic drugs,AEDs)致敏性的相关性。方法纳入75例AEDs致敏性的患者进行回顾性研究,同时纳入健康对照组60例。根据AEDs诱导的皮肤不良反应的临床表现的严重程度将病例分为轻型药疹组及高敏综合征组;根据致敏药物的数量将病例分为单药致敏组和多药致敏组。采用顺序特异性引物聚合酶链反应(PCR-SSP)检测以上患者和未服用过癫痫药物芳香族的30例正常对照者的HLA-B~*1502基因分型,采用Pearson分析HLA-B~*1502表达与AEDs致敏的相关性。结果 HLAB~*1502在芳香族(aromatic antiepileptic drugs,AEDs)致敏性中阳性表达例数要远高于阴性表达;多药致敏组HLAB~*1502基因阳性表达高于单药致敏组;抗癫痫药物高敏综合征组HLA-B~*1502基因阳性表达高于轻型药疹组;HLA-B~*1502表达水平越高,致敏药物越多。结论 HLA-B~*1502的表达与AEDs致敏性具有一定的相关性。
Objective To investigate the correlation between HLA-B~*1502 expression and sensitization of aromatic antiepileptic drugs( AEDs). Methods A retrospective study was conducted on 75 allergens of aromatic antiepileptic drugs( AEDs),and 60 healthy controls were included. According to the severity of the clinical manifestations of skin adverse events induced by AEDs,the cases were divided into light drug eruption group and anti-pain drug hypercholesterolemia group. The patients were divided into single drug sensitized group and multi-drug sensitized according to the number of sensitized drugs group. HLA-B~*1502 genotype was detected by sequential specific polymerase chain reaction( PCR-SSP) in 30 patients with normal controls who had not taken epilepsy drugs. Pearson analysis was used to analyze HLA-B~*1502 expression And AEDs. Results The positive expression of HLA-B~*1502 in the aromatherapy of aromatic antiepileptic drugs( AEDs) was much higher than that of negative expression. The positive expression of HLA-B~*1502 gene in multidrug-sensitized group was higher than that in single agent. The positive expression of HLA-B~*1502 was higher than that of light-type drug-eruption group. The positive expression of HLA-B~*1502 was correlated with sensitization of AEDs. Conclusion The high expression of HLA-B~*1502 in AEDs sensitization has a certain correlation with the number of sensitized drugs and the severity of clinical manifestations of skin adverse reactions.
Objective To investigate the correlation between HLA-B~*1502 expression and sensitization of aromatic antiepileptic drugs( AEDs). Methods A retrospective study was conducted on 75 allergens of aromatic antiepileptic drugs( AEDs),and 60 healthy controls were included. According to the severity of the clinical manifestations of skin adverse events induced by AEDs,the cases were divided into light drug eruption group and anti-pain drug hypercholesterolemia group. The patients were divided into single drug sensitized group and multi-drug sensitized according to the number of sensitized drugs group. HLA-B~*1502 genotype was detected by sequential specific polymerase chain reaction( PCR-SSP) in 30 patients with normal controls who had not taken epilepsy drugs. Pearson analysis was used to analyze HLA-B~*1502 expression And AEDs. Results The positive expression of HLA-B~*1502 in the aromatherapy of aromatic antiepileptic drugs( AEDs) was much higher than that of negative expression. The positive expression of HLA-B~*1502 gene in multidrug-sensitized group was higher than that in single agent. The positive expression of HLA-B~*1502 was higher than that of light-type drug-eruption group. The positive expression of HLA-B~*1502 was correlated with sensitization of AEDs. Conclusion The high expression of HLA-B~*1502 in AEDs sensitization has a certain correlation with the number of sensitized drugs and the severity of clinical manifestations of skin adverse reactions.
引文
[1]Chung WH,Hung SI,Chen YT.Genetic predisposition of life-threatening antiepileptic-induced skin reactions[J].Expert Opin Drug Saf,2010,9(1):15-21.
[2]Chong KW,Chan DW,Cheung YB,et al.Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status,and dose and treatment duration in paediatric neurology patients in Singapore[J].Arch Dis Child,2014,99(6):581-584.
[3]Kim SH,Lee KW,Song WJ,et al.Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans[J].Epilepsy Res,2011,97(1-2):190-197.
[4]Kaniwa N,Saito Y,Aihara M,et al.HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients[J].Epilepsia,2010,51(12):2461-2465.
[5]Mc Cormack M,Alfirevic A,Bourgeois S,et al.HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans[J].N Engl J Med,2011,364(12):1134-1143.
[6]Ozeki T,Mushiroda T,Yowang A,et al.Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population[J].Hum Mol Genet,2011,20(5):1034-1041.
[7]Wang XQ,Lang SY,Shi XB,et al.Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population[J].Seizure,2010,19(9):562-566.
[8]Zaccara G,Franciotta D,Perucca E.Idiosyncratic adverse reactions to antiepileptic drugs[J].Epilepsia,2007,48(7):1223-1244.
[9]Hu FY,Wu XT,An DM,et al.Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502allele in Chinese Han population[J].Seizure,2011,20(2):160-162.
[10]Shi YW,Min FL,Liu XR,et al.Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population[J].Basic Clin Pharmacol Toxicol,2011,109(1):42-46.
[11]Gogtay NJ,Bavdekar SB,Kshirsagar NA.Anticonvulsant hypersensitivity syndrome:a review[J].Expert Opin Drug Saf,2005,4(3):571-581.
[12]Lee KW,Park MH.New HLA nomenclature(2010)and its clinical application in Koreans[J].Korean J Lab Med,2010,30(3):203-217.
[13]Hung SI,Chung WH,Jee SH,et al.Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions[J].Pharmacogenet Genom,2006,16(4):297-306.
[14]Aihara M.Pharmacogenetics of cutaneous adverse drug reactions[J].J Dermatol,2011,38(3):246-254.
[15]王蕊艳,蔡兰云,付丽琴.抗癫痫药物皮肤不良反应与HLA-B*1502基因的相关性研究[J].中国医学创新,2014,2(34):20-22.
[16]Hung SI,Chung WH,Liu ZS,et al.Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese[J].Pharmacogenomics,2010,11(3):349-356.
[17]Lee KW,Oh DH,Lee C.Allelic and haplotypic diversity of HLAA,-B,-C,-DRB1,and-DQB1 genes in the Korean population[J].Tissue Antigens,2005,65(5):437-447.
[18]Lonjou C,Thomas L,Borot N,et al.A marker for Stevens-Johnson syndrome:ethnicity matters[J].Pharmacogenomics J,2006,6(4):265-268.
[2]Chong KW,Chan DW,Cheung YB,et al.Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status,and dose and treatment duration in paediatric neurology patients in Singapore[J].Arch Dis Child,2014,99(6):581-584.
[3]Kim SH,Lee KW,Song WJ,et al.Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans[J].Epilepsy Res,2011,97(1-2):190-197.
[4]Kaniwa N,Saito Y,Aihara M,et al.HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients[J].Epilepsia,2010,51(12):2461-2465.
[5]Mc Cormack M,Alfirevic A,Bourgeois S,et al.HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans[J].N Engl J Med,2011,364(12):1134-1143.
[6]Ozeki T,Mushiroda T,Yowang A,et al.Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population[J].Hum Mol Genet,2011,20(5):1034-1041.
[7]Wang XQ,Lang SY,Shi XB,et al.Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population[J].Seizure,2010,19(9):562-566.
[8]Zaccara G,Franciotta D,Perucca E.Idiosyncratic adverse reactions to antiepileptic drugs[J].Epilepsia,2007,48(7):1223-1244.
[9]Hu FY,Wu XT,An DM,et al.Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502allele in Chinese Han population[J].Seizure,2011,20(2):160-162.
[10]Shi YW,Min FL,Liu XR,et al.Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population[J].Basic Clin Pharmacol Toxicol,2011,109(1):42-46.
[11]Gogtay NJ,Bavdekar SB,Kshirsagar NA.Anticonvulsant hypersensitivity syndrome:a review[J].Expert Opin Drug Saf,2005,4(3):571-581.
[12]Lee KW,Park MH.New HLA nomenclature(2010)and its clinical application in Koreans[J].Korean J Lab Med,2010,30(3):203-217.
[13]Hung SI,Chung WH,Jee SH,et al.Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions[J].Pharmacogenet Genom,2006,16(4):297-306.
[14]Aihara M.Pharmacogenetics of cutaneous adverse drug reactions[J].J Dermatol,2011,38(3):246-254.
[15]王蕊艳,蔡兰云,付丽琴.抗癫痫药物皮肤不良反应与HLA-B*1502基因的相关性研究[J].中国医学创新,2014,2(34):20-22.
[16]Hung SI,Chung WH,Liu ZS,et al.Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese[J].Pharmacogenomics,2010,11(3):349-356.
[17]Lee KW,Oh DH,Lee C.Allelic and haplotypic diversity of HLAA,-B,-C,-DRB1,and-DQB1 genes in the Korean population[J].Tissue Antigens,2005,65(5):437-447.
[18]Lonjou C,Thomas L,Borot N,et al.A marker for Stevens-Johnson syndrome:ethnicity matters[J].Pharmacogenomics J,2006,6(4):265-268.