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
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), β = -0.021,P = 0.035)], highdensity
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 UA could be used as potential biomarkers
for the diagnosis of cerebral infarction.