| ObjectiveThis study aimed to evaluate the methylation status of matrix metalloproteinase-1(MMP-1)promoter in patients with chronic hepatitis B(CHB),and assess the potential association of MMP-1 promoter methylation in the progression of liver fibrosis.Patients and Methods137 patients with CHB,and 28 healthy controls(HCs)were included in our present study.The levels of liver fibrosis of the 137 patients with CHB was assessed by liver biopsy,there were 46 patients with SO,44 patients S1,24 patients with S2,17 patients with S3 and 6 patients with S4,and on the other hand,there were 19 patients with GO,68 patients with G1,32 patients with G2,13 patients with G3 and 5 patients with G4.We detected methylation status of serum MMP-1 promoter in serum from 137 patients with CHB and 28 HCs using methylation-specific polymerase chain reaction(MSP).Results1.We assayed the MMP-1 promoter methylation status in serum from 137 patients with CHB and 28 HCs.The age and gender were matched in both groups.However,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and Log10(HBV-DNA)were significantly higher in patients with CHB than those in HCs.2.The frequency of serum MMP-1 promoter methylation was significantly higher in patients with CHB(93/137,67.88%)than that in HCs(3/28,10.71%;?2=31.23,p<0.001).Interestingly,serum MMP-1 promoter methylation rate had a step-up trend with liver fibrosis progression.3.There were statistically significant differences between SO and S1(50%vs.70.45%,p=0.048),SO and S3-4(50%vs.95.65,p<0.001),S1 and S3-4(70.45%vs.96.65%,p = 0.016),S2 and S3-4(70.83%vs.96.65%,p = 0.023).However,there were no significant difference between SO and S2(50%vs.70.83%,p=0.091),S1 and S2(70.45%vs.70.83%,p = 0.974).4.MMP-1 promoter methylation frequencies among G0,G1,G2,and G3-4.There were statistically significant differences between GO and G2(47.37%vs.84.38%,p = 0.004),GO and G3-4(47.37%vs.88.89%,p<0.001),G1 and G2(60.29%vs.84.38%,p = 0.016),G1 and G3-4(60.29%vs.88.89%,p=0.022).However,the differences between GO and G1(47.37%vs.60.29%,p=0.319),G2 and G3-4(84.38%vs.88.89%,p=0.667)had not statistical significance.5.No correlation could be observed in age(p = 0.188),gender(p = 0.884),ALT(p = 0.081),AST(p = 0.142),HBeAg(p = 0.283)or Log10(HBV-DNA)(p = 0.355).6.The area under the receiver operating characteristic(ROC)curve(AUC)was 0.771(SE 0.0313,95%CI 0.692-0.839)for MMP-1 promoter methylation,which were higher than 0.653(SE 0.0503,95%CI 0.567-0.733)for APRI score(p = 0.041)ConclusionsIn conclusion,hypermethylation of MMP-1 promoter in patients with CHB was firstly explored in our study.And it was significantly correlation to fibrosis progression and inflammation grade,suggesting that MMP-1 promoter methylation might have its potential role in predicting liver fibrosis progression in patients with CHB. |
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