Abstract: Objective To detect p16 gene DNA methylation in the plasma of patients with systemic lupus erythematosus (SLE) and its significance in the disease activity and clinical manifestations.Methods Forty-five cases of SLE and 20 healthy controls were enrolled.Promoter methylation in p16 gene was measured by methylation specific PCR (MSP) in patients'plasma,and the correlation between the methylation status and clinical manifestations and routine laboratory findings were analyzed.Results Hypermethylation of p16 gene DNA was observed in the plasma of SLE.It was found that the rate of DNA hypermethylation was significantly higher in active SLE patients (20/24,83.33%) than that in inactive patients (9/21,42.85%) (x²=8.008 b;P<0.01),but not between the first onset SLE (71.43%,15/21) and recurrent SLE (58.33%,14/24) (P=0.371).DNA hyermethylation was detected in only one healthy control.The difference of the rate of DNA hyermethylation was significant between SLE patients (29/45,64.44%) and healthy individuals(1/20,5%) (x²=19.687,P<0.001).The SLE patients with hypermethylation of p16 gene seemed more susceptible to have arthritis (57.5%,15/26),leukopenia (42.3%,11/26) and elevated erythrocyte sedimentation rate (ESR)(56%,14/25) as compared with those without hypermethylation.A statistically significant correlation was found between the p16 gene hypermethylation and the presence of arthritis (P=0.019),leukopenia(P=0.016),and elevated ESR (P=0.026).Conclusions It is demonstrated that promoter methylation of p16 gene is significantly aberrant in SLE patients.From our study,p16 gene may be involved in the pathogenesis of SLE.It is suggested that there is a certain degree of relationship between DNA hypermethylation and the disease activity and clinical manifestations.

Key words: Lupus erythematosus,systemic, DNA methylation, Genes,p16