| Background:The nuclear transcription factor-κB(NF-κB)can regulate many immunological mediators’ expressions,so it plays a key role in controlling both innate immune response and adaptive immunity.The importance of NF-κB pathway has been revealed by accumulate evidences when the host immune responses were against Mycobacterium leprae in the development and progression of leprosy.Previous study have showed that many susceptibility genes have an affinity with NF-κB pathway,when we explored the function of the above genes,a close association between NF-κB pathway and the host immune responses against Mycobacterium leprae was founded in leprosy.However,particular association study between leprosy and NF-κB pathway associated gene has been never reported.Objective:To investigate whether there are more leprosy susceptibility loci in the NF-κB pathway related genes in Chinese population.Methods:We performed a large scale and two-stage candidate association study which 6413 healthy controls and 4631 leprosy cases were genotyped by using Sequenom MassArray system.The genotype-phenotype association was analyzed by using the logistic regression analysis with software Plink v1.07 in the validation stage.We also compared the expression of the filtered susceptibility gene between leprosy biopsy and healthy control skin through an unpublished RNA-sequence dataset(27 leprosy biopsy VS 18 healthy controls)using RNA-seq datasets and q-PCRResults:rs58744688 was significantly associated with leprosy(P=7.57×10-7,OR=1.12)by combining the previous GWAS datasets and the validation sample series of the current study.The SNP is located on FMNL1 gene and the NF-κB pathway related gene within this LD region was gene MAP3K14.Futhermore,FMNL1 was remarkably up regulated in the lesions of leprosy patients(P=5 × 10-5).Conclusion:A novel association at rs58744688(P=7.57× 10-7 OR=1.12)was identified.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. |
