30 Association and functional studies of genetic polymorphisms of MFG-E8 gene in systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor8 (MFG-E8) is a protein connects between v3 integrin of phagocytic macrophage and phosphatidylserine of apoptotic cell surface. In this study, we determine whether genetic variation of MFG-E8 gene and serum protein concentration are associated with SLE. Methods Single nucleotide polymorphisms (SNPs) were genotyped by three steps. At first, we used polymerase chain reaction in 20 patients with SLE and 20 normal controls (NC) for sequencing of a whole MFG-E8 gene in Korean population. Then we screened 12 selected SNPs in 55 SLE and 30 NC. Finally, we used Taq-man probe assay in 225 SLE and 230 NC for genotyping of targeted 5 SNPs. Furthermore, serum MFG-E8 concentrations were analysed in SLE. Results SLE patient‘s mean age was 35.7±7.8 years and 92% were women, which is not different form NC. rs2271715’s C allele and rs3743388’s G allele were shown higher frequency in SLE than NC (p=0.036, p=0.005, respectively). As the linkage disequilibrium test, rs1878326 and rs1878327 were shown high linkage (r2=0.879). Three haplotypes were found by four SNPs (rs4945, rs1878327, rs2271715, and rs3743388); AACG, CGCG, and CGTC. The CGCG haplotype was significantly higher in patients with SLE compared with NC (p=0.001, odds ratio=2.31). rs4945 was associated with erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibody, and systemic lupus erythematosus disease activity score. rs2271715 and rs3743388 were associated with renal disease, cumulated steroid dose, cyclophosphamide and mycophenolate mofetil usage and rs3743388 also was associated with anti-dsDNA antibody. Serum MFG-E8 concentration was shown significantly higher in SLE than NC (2,030.3±1,292.3 pg/mL vs 1,433.0±946.3 pg/mL, p=0.017). Conclusions Our data suggest possibility that MFG-E8 rs2271715 and rs3743388 SNP can be involved in susceptibility of SLE. Also, these SNPs are associated with renal disease and disease activity in SLE. Furthermore, rs4945 and rs1878327 polymorphisms may be a marker of disease activity. Funding Source(s): This research was supported by a grant of the Korea Health Technology R and D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI16C0992).