CORRELATION OF HYPERTENSION AND F2RL3 GENE METHYLATION WITH PROGNOSIS OF CORONARY HEART DISEASE
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
Authors: Gao, B. F.; Shen, Z. C.; Bian, W. S.; Wu, S. X.; Kang, Z. X.; Gao, Y.
Abstract
The aim of this work was to investigate the correlation between methylation of F2RL3 gene and coronary heart disease (CHD) with or without hypertension, secondary cardiovascular events and mortality. Sixty patients with CHD who underwent a cardiovascular rehabilitation program were recruited. Group A included 30 patients with hypertension and CHD, and group B included 30 patients with non-hypertensive CHD, followed-up for more than 8 years. F2RL3 gene methylation was characterized by Sequenom matrix assisted laser desorption ionization time flight mass spectrometry. The correlation between methylation of the F2RL3 gene, hypertension and secondary cardiovascular events and all-cause mortality was analyzed by multivariate Cox, regression models that estimated confounders to control risk ratios. The results showed that during the follow-up, 3 patients in Group A developed non-fatal stroke, 2 patients died of cardiovascular disease, 1 patient died of other causes, and 4 patients in Group B developed non-fatal myocardial infarction. After adjusting for known prognostic factors, Cox model analysis showed that methylation of F2RL3 gene was closely related to hypertension and mortality. After F2RL3 included in the regression model, the correlation between hypertension and all prognostic outcomes increased. In conclusion, the methylation of F2RL3 can affect the prognosis of different types of acute coronary syndrome and is closely related to mortality.
DNA methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons
CARCINOGENESIS
Authors: Alhamdow, Ayman; Lindh, Christian; Hagberg, Jessika; Graff, Pal; Westberg, Hakan; Krais, Annette M.; Albin, Maria; Gustavsson, Per; Tinnerberg, Hakan; Broberg, Karin
Abstract
Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 mu g/g creatinine) followed by chimney sweeps (0.34 mu g/g creatinine) and controls (0.05 mu g/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1 and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B = -2.04; P < 0.057, adjusted for smoking and age) and lower average AHRR methylation (B = -2.05; P < 0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B = -0.81; P < 0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.