HLA与疾病

HLA 与 疾 病,近年免疫遗传学表明免疫与遗传有关，基因表达量的异常可以引起免疫功能的紊乱，导致免疫性疾病的发生，这为探讨免疫性疾病的发病机制开辟了新途径。,遗传多态性是药物反应中个体差异的遗传基础，通过识别特定的多态基因型与药物疗效及毒性的关系，可为个体化治疗提供依据,Drugs and ADRs (药物与急性皮肤反应),SJS:Steven-Johnson综合症TEN:毒性皮肤坏死 (Toxic Epidermal Necrolysis),HLA-B*1502 Prevalent in Asia,The risk of SJS/TEN is estimated to be about 1 to 6 per 10,000 new users in countries with mainly Caucasian population.The risk increases about 10 times higher among Asian CountriesVariation within Asia ExistsGreater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia and parts of the PhilippinesSouth Asians, including the Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2 to 4%, but higher in some groupsHLA-B*1502 appears to be present at a low frequency, 1% in Japan and Korea,SJS/TEN:1-6/10,000人(白人发病率) 亚洲地区发病率高十倍 B*1502频率: 2-4% 东南亚地区,AP-SCAR in Japan and EU,Japan: all three AP-SCAR have HLA-B*5801EU: 61% AP-SCAR have HLA-B*5801,51位台湾AP-SCAR患者均发现有B*5801基因,Allopurinol and HLA-B*5801,Treat chronic gout by reducing uric acid to be produced by the body,51 AP-SCAR patients, (30 HSS, 13 SJS, 5 SJS/TEN and 3 TEN93 healthy subjects +135 tolerant patients (6 month with AP but no SCAR),A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs,Pharmacogenet Genomics. 2008 Feb;18(2):99-107,Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, Naldi L, Bouwes-Bavinck JN, Sidoroff A, de Toma C, Schumacher M, Roujeau JC, Hovnanian A, Mockenhaupt M; RegiSCAR study group,Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening cutaneous adverse reactions to drugs, especially to allopurinol, carbamazepine, lamotrigine, phenobarbital, phenytoine, sulfamethoxazole, oxicam and nevirapine.,RESULTS: Sixty-one percent of 31 allopurinol-induced SJS/TEN patients carried the HLA-B*5801 allele and the figure was 55% for 27 patients of European ancestry odds ratio=80 (34-187), (P10(-6) as previously observed in Han Chinese. For other drugs, two rare alleles showed a weaker association with SJS/TEN in a limited number of patients: B*38 for sulfamethoxazole or lamotrigine-related patients, and B*73 for oxicam.,Of race,ethnicity,and rash: the genetics of antiepileptic drug-induced skin reactions,RECENT FINDINGS: Several recent studies have reported strong genetic associations between HLA alleles and susceptibility to drug hypersensitivity. The genetic associations can be drug specific, such as HLA-B*1502 being associated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), HLA-B*5701 with abacavir hypersensitivity and HLA-B*5801 with allopurinol-induced severe cutaneous adverse reactions. A genetic association can also be phenotype-specific, as B*1502 is associated solely with carbamazepine-SJS/TEN, and not with either maculopapular eruption or hypersensitivity syndrome. Furthermore, a genetic association can also be ethnicity specific; carbamazepine-SJS/TEN associated with B*1502 is seen in south-east Asians but not in whites, which may be explained by the different allele frequencies.,Human leukocyte antigens and drug hypersensitivity,Curr Opin Allergy Clin Immunol. 2007 Aug;7(4):317-23.,Chung WH, Hung SI, Chen YT,Am J Hum Genet. 2008 Aug;83(2):219-27. Epub 2008 Jul 24.,Mol Immunol. 2008 May;45(9):2429-36. Epub 2008 Mar 4,Virol J. 2009 May 1;6:46,（HLA-DQ2 or HLA-DQ8）,Can J Gastroenterol. 2006 Sep;20(9):571-3.,J Neurosci Res. 2004 Oct 1;78(1):100-14,Pain. 2009 Jun 10.,Pharmacogenomics,Nippon Rinsho. 2009 Jun;67(6):1175-9,Saito Y, Sawada J,In this review, we would like to outline the recent progress in pharmacogenomics, focusing on anti-cancer drugs tegafur (with reference to CYP2A6 polymorphisms), irinotecan (UGT1A1), and cetuximab (somatic mutations in KRAS), and an anti-platelet drug clopidogrel (CYP2C19). This review also addresses genetic markers for drug-induced severe cutaneous adverse reactions (HLA-B) and myopathy(SLCO1B1).,第四届全国免疫遗传学研讨会HLA与疾病相关联的新进展,南方医科大学南方医院移植配