| Background and ObjectiveIschemic stroke is the most common disease in neurology,and it is also the leading cause of death and disability in adults.It is important to find its pathogenic mechanism and find suitable predictive indicators in more aspects.Diseases such as Alzheimer's disease,Parkinson's disease,and demyelination are more frequently studied in genetics,but there are relatively few studies on ischemic stroke.Nicotinamide phosphoribosyl transferase(NAMPT)gene and paraoxonase(PON)family genes are believed to be closely associated with the pathogenesis of ischemic stroke,and telomere length is also associated with cardiovascular and cerebrovascular diseases.This study was to evaluate the association between the level of DNA methylation in the promoter region of NAMPT gene,PON family genes(PON1,PON2 and PON3)and the DNA sequence-telomere length at the end of chromosome in patients with ischemic stroke,and further explore the possibility of using it as a potential biomarker.Materials and methodsIn this study,Case-control studies were used,152 patients with confirmed ischemic stroke were selected as the case group,and 152 sex and age-matched healthypersons were selected as control group.The quantitative methylation-specific PCR(q MSP)was used to determine the promoter methylation levels of NAMPT?PON1?PON2?PON3 genes and detected the absolute telomere length.The methylation level was expressed as a methylation reference percentage(PMR:%).ResultsThe methylation level of NAMPT gene in both case and control samples was very low(case: 24.59% vs control 19.69%,P = 0.551),and there was no significant difference in the level of methylation between the two groups.The methylation level of PON2 gene in both case and control was almost 0%.The PON1 methylation level(%)in the case group was significantly higher than that in the control group(Z =-3.898,P = 0.0001).The methylation level of PON3(%)in the case group was significantly lower than that in the control group(Z =-3.098,P = 0.002).Sex subgroup showed that the difference between PON1 and PON3 was more significant in males(PON1,Z =-3.786,P = 0.0002;PON3,Z =-2.709,P = 0.007).Telomere length in the case group was significantly lower than that in the control group(Z =-11.843,P < 0.0001),and there was no significant gender difference.There was a significant correlation between PON1 and PON3 methylation level(case: r = 0.418,P= 0.0001;control: r = 0.3,P = 0.0002).However,no correlation was found between PON1,PON3 methylation level with telomere length(case: r = 0.023,P = 0.775;control: r =-0.157,P = 0.054).Multiple logistic regression analysis of the risk of ischemic stroke,it was suggested that the elevated methylation level of PON3 is a protective factor of ischemic stroke[OR(95% CI)= 0.979(0.96-0.999),P = 0.035)],telomere length was a protective factor of ischemic stroke[OR(95% CI)= 0.748(0.681-0.823),?=-0.29,P< 0.0001].The receiver operating characteristic(ROC)curve analysis for the diagnostic value of methylation level of PON3 and telomere length in ischemic stroke.The results showed that the AUC of PON3 methylation was 0.605,95%CI=0.541-0.669,sensitivity = 88.7%,specificity = 35.5%,cut off = 17.97 7,P = 0.002;The AUC of telomere length was 0.894,95% CI=0.851-0.937,Sensitivity = 84.7%,specificity = 93.4%,Cut off = 0.0473,P < 0.0001.ConclusionsThe methylation level in the promoter region of NAMPT,PON2 were not related tothe pathogenesis of ischemic stroke.Hypermethylation of PON1 gene and hypomethylation of PON3 gene were associated with the risk of ischemic stroke in male patients.Shorter telomere length was associated with the risk of ischemic stroke,and not have the gender differences.PON1 and PON3 methylation may interact with each other.But there was no significant correlation between the methylation level of PONs genes and telomere length.The methylation level of PON3 has low diagnostic value for ischemic stroke.Telomere length can be used as a potential diagnostic marker for ischemic stroke. |
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