title: Genetic polymorphism in milk fat globule-EGF factor 8 (MFG-E8) is associated with systemic lupus erythematosus in human.
abstract: 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 (3(Arg or Ser)) and 76 (76(Leu or Met)) did not show genetic linkage. Genetic polymorphism on MFG-E8 residue 76 correlated significantly to SLE. The MFG-E8-76(Met) allele predisposed subjects to SLE in a recessive mode (odds ratio: 2.1, P = 0.020), while carriage of MFG-E8-76(Leu) were negatively associated with SLE. The MFG-E8 genotypic combinations with 3(Ser) and 76(Leu) showed the most pronounced protective effect on SLE when compared to the most predisposing genotype 3(Arg/Arg)-76(Met/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.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: C Y
authors.initials: CY
authors.lastname: Hu
authors.forename: C S
authors.initials: CS
authors.lastname: Wu
authors.forename: H F
authors.initials: HF
authors.lastname: Tsai
authors.forename: S K
authors.initials: SK
authors.lastname: Chang
authors.forename: W I
authors.initials: WI
authors.lastname: Tsai
authors.forename: P N
authors.initials: PN
authors.lastname: Hsu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000378:metabolism; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins