Objective: Paraoxonase (PON) family genes are closely related to the etiology and prognosis of cerebral infarction. This study explored the association of the promoter methylation of PON family genes (PON1, PON2 and PON3) with the risk of cerebral infarction. Materials and Methods: In this study, 152 patients with confirmed cerebral infarction were selected as the case group, and 152 healthy controls were selected as the control group. The quantitative methylation-specific PCR (qMSP) was used to determine the promoter methylation levels of PON1, PON2 and PON3 genes. The methylation level was expressed as a methylation reference percentage (PMR). Results: Our results indicated that PON1 methylation was significantly higher in the case group than in the control group (P = 0.0001). On the contrary, PON3 methylation was significantly lower in the case group than in the control group (P = 0.002). In addition, we found that PON2 gene had a very low level of methylation in both case and control groups (PMR = 0). Subgroup analysis showed that PON1 and PON3 methylation were associated with cerebral infarction only in males (PON1, P = 0.0002; PON3, P = 0.007). Interestingly, the methylation levels of PON1 and PON3 were correlated with each other (case: r = 0.418, P = 0.0001; control: r = 0.3, P = 0.0002). Further multiple regression analysis suggested that elevated methylation levels of PON3 were a protective factor for cerebral infarction [OR (95%CI) = 0.979 (0.96, 0.999), beta = -0.021, P = 0.035)], high-density lipoprotein (HDL) and uric acid (UA) also were protective factors for cerebral infarction [HDL, OR (95% CI) = 0.01 (0.003, 0.033), P < 0.0001); UA, OR (95% CI) = 0.995 (0.991, 0.998), P = 0.003)]. The ROC curve analysis found that the combination of PON3. HDL, and UA had a good predictive power for cerebral infarction (AUC=0.878, 95% CI=0.839-0.918, sensitivity 73.7%, specificity 89.7%, P < 0.0001). Conclusion: PON1 and PON3 promoter methylation levels in peripheral blood were closely related. PON1 and PON3 methylation were associated with the risk of cerebral infarction in men. PON3 promoter methylation combined with HDL and ILIA could be used as potential biomarkers for the diagnosis of cerebral infarction.
[1]Zhengzhou Univ, Dept Neurol, Affiliated Hosp 2, Zhengzhou 450014, Henan, Peoples R China;
[2]Fudan Univ, Shanghai Pudong Hosp, Dept Neurol, Pudong Med Ctr, Shanghai 201399, Peoples R China;
[3]Zhengzhou Univ, Dept Neurol, Zhengzhou Cent Hosp, Zhengzhou 450000, Henan, Peoples R China;
[4]148th Hosp PLA, Dept Neurol, Zibo 255330, Shandong, Peoples R China;
[5]Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China
(8.0+极速模式)