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A pathway‐based association analysis identified FMNL1‐MAP3K14 as susceptibility genes for leprosy
Authors:Huimin Zhang  Zhenzhen Wang  Xi'an Fu  Yonghu Sun  Zihao Mi  Gongqi Yu  Lele Sun  Na Wang  Chuan Wang  Qing Zhao  Qing Pan  Zhenhua Yue  Hong Liu  Furen Zhang
Affiliation:1. Binzhou Medical University, Yantai, Shandong, China;2. Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China;3. Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, Shandong, China;4. School of Medicine, Shandong University, Jinan, Shandong, China;5. School of Medicine and Life Science, University of Jinan‐Shandong Academy of Medical Sciences, Jinan, Shandong, China;6. Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, Shandong, China;7. National Clinical Key Project of Dermatology and Venereology, Jinan, Shandong, China
Abstract: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 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 genomewide association data sets 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.
Keywords:   FMNL1     Leprosy     MAP3K14        Mycobacterium Leprea     NF‐κ  B
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