A Pathway-Based Association Analysis Identified FMNL1-MAP3K14 as Susceptibility Genes for Leprosy

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 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.

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