01836nas a2200313   4500000000100000008004100001653001100042653001200053653001400065653001200079653001000091100001200101700001100113700000900124700001000133700000900143700000900152700001000161700001100171700001100182700001100193700001000204700001000214700001000224700001200234245010300246520115900349022001401508       2017                            d10aNF-κB10aMAP3K1410aM. Leprea10aleprosy10aFMNL11 aZhang H1 aWang Z1 aFu X1 aSun Y1 aMi Z1 aYu G1 aSun L1 aWang N1 aWang C1 aZhao Q1 aPan Q1 aYue Z1 aLiu H1 aZhang F00aA pathway-based association analysis identified FMNL1-MAP3K14 as susceptibility genes for leprosy.3 a<p>The nuclear transcription factor-κB (NF-κB) plays a pivotal role in controlling both innate and adaptive immunity and regulates the expressions of many immunological mediators. Abundant evidences have showed that the importance of NF-κB pathway in the host immune responses against Mycobacterium leprae in the development of leprosy. However, no particular association study between leprosy and NF-κB pathway related gene polymorphisms was reported. Here, we performed a large scale and two-stage candidate association study to investigate the association between 94 NF-κB pathway related genes and leprosy. Our results showed that rs58744688 was significantly associated with leprosy (P=7.57×10-7 , OR=1.12) by combining the previous genome wide association datasets and four independent validation sample series, consisting of a total of 4631 leprosy cases and 6413 healthy controls. This founding implicated that MAP3K14 and FMNL1 were susceptibility genes for leprosy, which suggested the involvement of macrophage targeting and NF-κB pathway in the development of leprosy. This article is protected by copyright. All rights reserved.</p>
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