Role of the PON polymorphisms on progression of chronic hepatitis and cirrhosis
TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI
Authors: Aldirmaz, Mevlut; Altintas, Nuray; Var, Ahmet; Ellidokuz, Ender
Abstract
Aim and Background: The probable role of PON1-192, PON1-55, PON2-148, PON2-311 polymorphisms of the PON enzyme family, which are play a role in antioxidant pathways in the progression of chronic hepatitis to cirrhosis was investigated. Methods: The patient population included 64 chronic hepatitis patients without cirrhosis and 30 patients with cirrhosis which were diagnosed by biopsy compared to a control group (n=68) of normal healthy volunteers. All patients were recruited from the outpatient clinic of Gastroenterology, Celal Bayar University Faculty of Medicine. Genomic DNA of leukocytes was isolated by using a commercial isolation kit. PCR analysis was assessed for PON1-192, PON1-55, PON2-148, PON2-311 genotypes and the products digested with HinfI restriction enzyme to see the allelic polymorphisms. The PCR products were resolved on electrophoresis 2% agarose gel and visualized with a Syngene (USA) image analysis system. Odds ratios in 95% confidence interval were calculated for the two genotypes. For the statistical analyses SPSS version 10.0 was used. Results: The prevalence of PON1-192, PON1-55, PON2-148 genotypes were very different between the groups but was not statistically significant. The frequency of the "SS" and "SC" genotypes of PON2-311 in patients with hepatitis and cirrhosis was higher than the control group and their Odds Ratios were statistically significant. Conclusion: The prevalence of PON2 gene "SS" and "SC" genotypes of in patients was higher than that of healthy volunteers (ORs were 3,855 and 2,404 respectively). Similarly SS" and "SC" genotypes of in patients with cirrhosis was higher than that of patients with hepatitis (ORs were 3,436 and 2,223 respectively) These results suggested that the "SS" and "SC" genotypes of PON2 gene might cause a susceptibility for developing of hepatitis and progression of this condition to cirrhosis. It can be also speculated that "CC" genotype may be protective for the progression of disease.
PON1 Hypermethylation and PON3 Hypomethylation are Associated with Risk of Cerebral Infarction
CURRENT NEUROVASCULAR RESEARCH
Authors: Xiao, Jianhao; Li, Xiaodong; Yuan, Qian; Zhang, Simiao; Qu, Kun; Wu, Boyi; Wang, Yunliang; Duan, Shiwei
Abstract
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.