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hla-dqa1–hla-drb1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants

长期以来科学家们一直认为大约会有4%常服用炎性肠病药物的患者容易患胰腺炎,而本文研究中,研究者鉴别出了这些患者群体特殊的遗传组成,结果表明其患胰腺炎的可能性是正常个体的四倍

研究者heap说道,我们的研究伙伴遍布全世界,我们一直在寻找有效的检测方法,来预测哪些病人更容易引发严重的药物副作用;如今我们鉴别出了容易引发胰腺炎的易感患者人群,我们希望新型的检测技术被开发制作成一种工具盒来进行dna检重症胰腺炎的治疗测,预测治疗疾病的药物给患者带来的副作用,比如治疗肝脏损伤的药物会给患者带来什么样的副作用等,如果可以开发出这种工具,那么研究者就会利用它们来鉴别出更多的风险个体来挽救其生命(生物谷bioon.com)

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doi:10.1038/ng.3093

pmc:

pmid:

2014年9月16日 讯 /生物谷bioon/ --近日,来自埃克塞特大学等处的研究人员通过研究发现,携带特殊遗传突变的病人,如果广泛用药的话,其患胰腺炎的风险是正常个体的四倍,相关研究成果刊登于国际著名杂志nature genetics上

pancreatitis occurs in approximately 4% of胰腺炎应注意什么 patients treated with the thiopurines azathioprine or mercaptopurine. its development is unpredictable and almost always leads to drug withdrawal. we identified patients with inflammatory bowel disease (ibd) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the 胰腺炎喝茶world. after detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with ibd. we identified strong evidence of association within the class ii hla region, with the most significant association identified at rs (odds ratio 2.59, 95% confidence interval 2.07–3.26, p = 2 × 水泡胰腺炎10−16). we replicated these findings in an independent set of 78 cases and 472 controls with ibd matched for drug exposure. fine mapping of the hla region identified association with the hla-dqa1*02:01–hla-drb1*07:01 haplotype. patients heterozygous at rs have a 9% risk of developing pancreatitis after administration of a 胆囊切除 胰腺炎thiopurine, whereas homozygotes have a 17% risk.

文章中,研究者graham heap表示,在携带有两个特殊遗传标记拷贝的病人中,如果其经常服用硫嘌呤类药物的话,有17%的个体就很有可能会患胰腺炎;硫嘌呤类药物包括硫唑嘌呤和巯嘌呤,这些药物是常用于有效抑制机体免疫系统来治疗炎性肠病、风湿性关节炎等疾病的药物

graham a heap, michael n weedon, claire m bewshea, abhey singh, mian chen, jack b satchwell, julian p vivian, kenji so, patrick c胰腺炎积水 dubois, jane m andrews, vito annese, peter bampton, martin barnardo, sally bell, andy cole, susan j connor, tom creed, fraser r cummings, mauro d"amato, tawfique k daneshmend, richard n fedorak, timothy h florin, daniel r gaya, emma greig, jonas halfvarson et al.