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Objective: Systemic lupus erythematosus is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family. To date, association between ET-1 and pathogenesis of SLE remains unclear. Method: This case-control study was carried out by 314 SLE, 252 other inflammatory autoimmune diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with KASP. Results: Raised ET-1 concentrations in SLE patients correlated with clinical characteristics. Serum CCN3, IL-28B expressions were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with pericarditis, pyuria and fever manifestations. Rs3087459 (CC) and rs9369217 (TC) were relevant to anti-SSB indicator. Rs5369 (AA) was associated with IgG and CRP levels. Conclusion: elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were relevant to SLE susceptibility.