Genetic polymorphism in milk fat globule-EGF factor 8 (MFG-E8) is associated with systemic lupus erythematosus in human
Journal
Lupus
Journal Volume
18
Journal Issue
8
Pages
676-681
Date Issued
2009
Author(s)
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 (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.
SDGs
Other Subjects
arginine; lactadherin; leucine; methionine; serine; adolescent; adult; aged; amino acid substitution; article; case control study; controlled study; female; gene frequency; gene function; genetic association; genetic linkage; genetic polymorphism; genetic predisposition; genetic variability; genotype; human; human cell; major clinical study; male; priority journal; sequence analysis; single nucleotide polymorphism; systemic lupus erythematosus; Taiwan; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antigens, Surface; Base Sequence; Case-Control Studies; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Genotype; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Milk Proteins; Molecular Sequence Data; Phagocytes; Polymorphism, Genetic; Young Adult
Type
journal article