Genetic polymorphism in milk fat globule-EGF factor 8 (MFG-E8) is associated with systemic lupus erythematosus in human

C. Y. Hu, C. S. Wu, H. F. Tsai, S. K. Chang, W. I. Tsai, Ping Ning Hsu

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Milk fat globule-EGF factor 8 (MFG-E8) is a molecule implicated in phagocytic clearance of apoptotic cells by bridging between macrophages and apoptotic cells. Defects in MFG-E8 cause lupus-like disease in murine models. The aim of our study is to determine whether genetic variation in MFG-E8 predisposes human to systemic lupus erythematosus (SLE). A case-control study of MFG-E8 genetic polymorphism was performed on 147 SLE patients and 146 non-lupus control subjects. Single nucleotide polymorphisms (SNPs) in the coding sequence of human MFG-E8 gene were investigated. SNPs on MFG-E8 residues 3 (3ArgorSer) and 76 (76LeuorMet) did not show genetic linkage. Genetic polymorphism on MFG-E8 residue 76 correlated significantly to SLE. The MFG-E8-76Met allele predisposed subjects to SLE in a recessive mode (odds ratio: 2.1, P = 0.020), while carriage of MFG-E8-76Leu were negatively associated with SLE. The MFG-E8 genotypic combinations with 3Ser and 76Leu showed the most pronounced protective effect on SLE when compared to the most predisposing genotype 3Arg/Arg-76Met/Met (OR: 0.29, P = 0.007). According to our result, MFG-E8 is associated with SLE predisposition in Taiwanese. Our study implicates that the impairment of phagocytic clearance of apoptotic cells through phosphotidylserine-dependent MFG-E8 system may lead to the development of human SLE.

Original languageEnglish
Pages (from-to)676-681
Number of pages6
Issue number8
Publication statusPublished - 2009



  • Apoptosis
  • Genetic polymorphism
  • Milk fat globule-EGF factor 8 (MFG-E8)
  • Single nucleotide polymorphisms
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology

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