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Objective: Milk fat globule-EGF factor 8(MFG-E8) facilitates the phagocytosis of apoptotic cells by bridging the apoptotic cells and phagocytes.MFG-E8-/-mice spontaneously develop a systemic lupus erythematous(SLE)-like autoimmune disease, which is associated with an impaired clearance of apoptotic cells.The aim of this study was to explore whether polymorphisms in the MFG-E8 gene were associated with susceptibility to SLE.Methods: Two polymorphisms in MFG-E8 (rs4945 C>A and rs1878326 C>A) were analyzed by polymerase chain reaction restriction fragment length polymorphism in 173 SLE patients and 170 controls.Association between the MFG-E8 plasmaconcentration and rs1878326 genotype was analyzed.Result: The polymorphism rs1878326 C>A of MFG-E8 gene was found to be associated with susceptibility to SLE in the central China Han Population(C allele vs A allele : adjusted OR=0.678, 95% CI:0.495-0.930, P =0.016), while rs4945 was not(C allele vs A allele : adjusted OR=0.923, 95%CI:0.587-1.450, P=0.728).The rs1878326 A allele and CA genotype decreases the risk of SLE(adjusted OR=0.678 ; 95% CI:0.495-0.930; P =0.016 and adjusted OR=0.415, 95% CI:0.210-0.819, P=0.011), which is similar to William Raoul s report, showing that genetic variations of the MFG-E8 gene contribute to SLE susceptibility among different populations.In addition, we revealed that the rs1878326 C>A genotype did not affect the plasma MFG-E8 concentration in the patients(n=89, F=1.611, p=0.206).Conclusion: Based on genetic evidence, we conclude that the rs1878326 C>A polymorphism of MFG-E8 gene was associated with susceptibility to SLE in Chinese Han Population.However, rs187836 C>A may not affect the plasma concentration of MFG-E8.The results were based on a limited sample size and larger well-designed studies are warranted to verify these findings.