Objective To analyze the whole genomic DNA methylation level and estrogen receptor α (ERα) gene promoter methylation status in systemic lupus erythematosus (SLE) with atherosclerosis (AS) in model mouse,and to explore its role in the pathogenesis of SLE with AS.Methods Eleven apoE-/-C57BL/6 mice were randomly divided into the model group (SLE+AS group) and the control group (AS group).Eleven wild C57BL/6 mice were also randomly divided into the model group (SLE group) and the control group (blank group).Single intraperitoneal injection of pristane 0.5 ml for the model group,single intraperitoneal injection of normal saline 0.5 ml for the control group.Eight months after injection,all mice were sacrificed,genomic DNA was extracted from spleen.The total genomic DNA methylation level was detected,and pyrosequencing was performed to determine the methylation status of ERα gene promoter.The differences between groups were compared.ANOVA,LSD-t test,Tamhane's T2 test were used for statistical analysis.Results The total genomic DNA methylation levels were (4.7±1.5)％,(5.1±0.5)％,(6.6±1.6)％,(7.5±1.6)％ respectively in the SLE+AS group,AS group,SLE group,blank group respectively,the average methylation indices of ERα gene promoter were (13.0±3.1)％,(26.7±7.2)％,(15.7±3.8)％ and (21.4±4.2)％ respectively.The total genomic DNA methylation level and the average methylation index of ERα gene promoter in the SLE+AS group and the SLE group was significantly lower than that of the blank group (P＜0.05).Compared with the AS group,the total genomic DNA methylation levels and the average methylation index of ERα gene promoter in the SLE+AS group were significantly decreased (P＜0.05).Conclusion The total genomic DNAs and the ERα gene promoters in SLE with AS model mouse are in low-methylation status.The results of this study suggest that epigenetics may play an important role in the pathogenesis of SLE with AS.