PON1 Hypermethylation and PON3 Hypomethylation are Associated with Risk of Cerebral Infarction
| Autor: | Boyi Wu, Kun Qu, Jianhao Xiao, Simiao Zhang, Qian Yuan, Shiwei Duan, Xiaodong Li, Yunliang Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Gastroenterology 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Developmental Neuroscience Risk Factors Internal medicine medicine Humans Promoter Regions Genetic Aged biology Cerebral infarction business.industry Aryldialkylphosphatase Paraoxonase Methylation Cerebral Infarction DNA Methylation Middle Aged medicine.disease PON1 030104 developmental biology Neurology chemistry DNA methylation biology.protein Etiology Uric acid Female business 030217 neurology & neurosurgery Biomarkers Lipoprotein |
| Zdroj: | Current neurovascular research. 16(2) |
| ISSN: | 1875-5739 |
| Popis: | 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), 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. |
| Databáze: | OpenAIRE |
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