A pathway-based association analysis identified FMNL1-MAP3K14 as susceptibility genes for leprosy

Exp Dermatol. 2018 Mar;27(3):245-250. doi: 10.1111/exd.13490. Epub 2018 Feb 8.

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; MAP3K14; Mycobacterium Leprea; Leprosy; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cytoskeletal Proteins / genetics*
  • Female
  • Formins
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Leprosy / genetics*
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • NF-kappaB-Inducing Kinase
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / genetics*

Substances

  • Cytoskeletal Proteins
  • FMNL1 protein, human
  • Formins
  • NF-kappa B
  • Protein Serine-Threonine Kinases