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NEJM：张福仁团队发现麻风致死性药物氨苯砜敏感基因

2013-10-30 桂园 中国广播网

张福仁麻风病
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山东省医学科学院24日宣布，山东省皮肤病研究所张福仁研究团队通过对2042个病例及健康对照者的研究，成功定位氨苯砜综合症的风险位点基因。氨苯砜综合症是导致麻风病死亡的主要原因之一，该位点的发现和临床应用，可有效预防氨苯砜综合症发生，使麻风病的一级预防成为可能。 据介绍，张福仁研究团队致力于麻风防治研究十年，共发现12个麻风易感基因，研究结果先后发表于《新英格兰医学杂志》、《自然？遗传学》

山东省医学科学院24日宣布，山东省皮肤病研究所张福仁研究团队通过对2042个病例及健康对照者的研究，成功定位氨苯砜综合症的风险位点基因。氨苯砜综合症是导致麻风病死亡的主要原因之一，该位点的发现和临床应用，可有效预防氨苯砜综合症发生，使麻风病的一级预防成为可能。

据介绍，张福仁研究团队致力于麻风防治研究十年，共发现12个麻风易感基因，研究结果先后发表于《新英格兰医学杂志》、《自然.遗传学》和《美国人类遗传学杂志》等国际著名学术期刊。结合麻风易感基因研究成果，他们认为氨苯砜综合症的发生主要决定于患者的遗传易感性，即患者可能携带一个或多个风险基因位点。如能发现该位点并用于风险预测，就能实现有效预防。

该研究团队首次采用全基因组关联技术和目标区域测序技术，历时三年对2042个氨苯砜综合症患者和对照进行基因分型和联合分析，成功定位氨苯砜综合症的风险位点HLA-B*1301，该位点的敏感度和特异度分别达86.8%、85.7%，如果某人具有一个HLA-B*1301风险等位基因，则其使用氨苯砜后发生重症药物不良反应的风险是不具有这一基因的人的37.5倍；具有两个HLA-B*1301风险等位基因，其使用氨苯砜后发生药物不良反应的风险增长到110.8倍。该位点的发现和临床应用，可有效预防氨苯砜综合症发生。同时，通过对其它氨苯砜适应症患者做用药前检测，可以满足艾滋病并发症、疟疾等多种传染性疾病的用药安全，使氨苯砜的临床应用大大拓展。

原始出处：
Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ, Yu YX, Chen MF, Low HQ, Li JH, Bao FF, Foo JN, Bei JX, Jia XM, Liu J, Liany H, Wang N, Niu GY, Wang ZZ, Shi BQ, Tian HQ, Liu HX, Ma SS, Zhou Y, You JB, Yang Q, Wang C, Chu TS, Liu DC, Yu XL, Sun YH, Ning Y, Wei ZH, Chen SL, Chen XC, Zhang ZX, Liu YX, Pulit SL, Wu WB, Zheng ZY, Yang RD, Long H, Liu ZS, Wang JQ, Li M, Zhang LH, Wang H, Wang LM, Xiao P, Li JL, Huang ZM, Huang JX, Li Z, Liu J, Xiong L, Yang J, Wang XD, Yu DB, Lu XM, Zhou GZ, Yan LB, Shen JP, Zhang GC, Zeng YX, de Bakker PI, Chen SM, Liu JJ. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med. 2013 Oct 24;369(17):1620-8.

Liu H, Bao F, Irwanto A, Fu X, Lu N, Yu G, Yu Y, Sun Y, Low H, Li Y, Liany H, Yuan C, Li J, Liu J, Chen M, Liu H, Wang N, You J, Ma S, Niu G, Zhou Y, Chu T, Tian H, Chen S, Zhang X, Liu J, Zhang F. An association study of TOLL and CARD with leprosy susceptibility in Chinese population. Hum Mol Genet. 2013 Nov 1;22(21):4430-7

Liu H, Irwanto A, Tian H, Fu X, Yu Y, Yu G, Low H, Chu T, Li Y, Shi B, Chen M, Sun Y, Yuan C, Lu N, You J, Bao F, Li J, Liu J, Liu H, Liu D, Yu X, Zhang L, Yang Q, Wang N, Niu G, Ma S, Zhou Y, Wang C, Chen S, Zhang X, Liu J, Zhang F.Identification of IL18RAP/IL18R1 and IL12B as leprosy risk genes demonstrates shared pathogenesis between inflammation and infectious diseases. Am J Hum Genet. 2012 Nov 2;91(5):935-41

Zhang F, Liu H, Chen S, Low H, Sun L, Cui Y, Chu T, Li Y, Fu X, Yu Y, Yu G, Shi B, Tian H, Liu D, Yu X, Li J, Lu N, Bao F, Yuan C, Liu J, Liu H, Zhang L, Sun Y, Chen M, Yang Q, Yang H, Yang R, Zhang L, Wang Q, Liu H, Zuo F, Zhang H, Khor CC, Hibberd ML, Yang S, Liu J, Zhang X.Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy. Nat Genet. 2011 Oct 23;43(12):1247-51.

Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, Cui Y, Yan XX, Yang HT, Yang RD, Chu TS, Zhang C, Zhang L, Han JW, Yu GQ, Quan C, Yu YX, Zhang Z, Shi BQ, Zhang LH, Cheng H, Wang CY, Lin Y, Zheng HF, Fu XA, Zuo XB, Wang Q, Long H, Sun YP, Cheng YL, Tian HQ, Zhou FS, Liu HX, Lu WS, He SM, Du WL, Shen M, Jin QY, Wang Y, Low HQ, Erwin T, Yang NH, Li JY, Zhao X, Jiao YL, Mao LG, Yin G, Jiang ZX, Wang XD, Yu JP, Hu ZH, Gong CH, Liu YQ, Liu RY, Wang DM, Wei D, Liu JX, Cao WK, Cao HZ, Li YP, Yan WG, Wei SY, Wang KJ, Hibberd ML, Yang S, Zhang XJ, Liu JJ. Genomewide association study of leprosy. N Engl J Med. 2009 Dec 31;361(27):2609-18.

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    2023-05-19 侠胆医心 来自上海

    #氨苯砜综合症#是导致#麻风病#死亡的主要原因之一，该位点的发现和临床应用，可有效预防#氨苯砜#综合症发生，使麻风病的一级预防成为可能。

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2137780, encodeId=9718213e780b0, content=<a href='/topic/show?id=75ad10625421' target=_blank style='color:#2F92EE;'>#氨苯砜综合症#</a>是导致<a href='/topic/show?id=6e9f103104b9' target=_blank style='color:#2F92EE;'>#麻风病#</a>死亡的主要原因之一，该位点的发现和临床应用，可有效预防<a href='/topic/show?id=da4264064ad' target=_blank style='color:#2F92EE;'>#氨苯砜#</a>综合症发生，使麻风病的一级预防成为可能。, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=106254, encryptionId=75ad10625421, topicName=氨苯砜综合症), TopicDto(id=103104, encryptionId=6e9f103104b9, topicName=麻风病), TopicDto(id=64064, encryptionId=da4264064ad, topicName=氨苯砜)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Fri May 19 01:44:22 CST 2023, time=2023-05-19, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=1928592, encodeId=ae2d192859267, content=<a href='/topic/show?id=9d375e53252' target=_blank style='color:#2F92EE;'>#敏感基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57532, encryptionId=9d375e53252, topicName=敏感基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8346212, createdName=respect, createdTime=Tue Feb 11 05:04:00 CST 2014, time=2014-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568233, encodeId=46fc156823380, content=<a href='/topic/show?id=569d8644eb9' target=_blank style='color:#2F92EE;'>#致死性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86447, encryptionId=569d8644eb9, topicName=致死性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae1815335551, createdName=andy2092, createdTime=Fri Nov 01 04:04:00 CST 2013, time=2013-11-01, status=1, ipAttribution=)]
    2014-02-11 respect

    #敏感基因#

    0

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    2013-11-01 andy2092

    #致死性#

    0