AIMS: In a recent genome-wide study, cytosine bases in the F2RL3 gene, which codes for a protein relevant for cardiovascular physiology, were discovered to be hypomethylated in smokers. We aimed to determine the clinical importance of methylation at the F2RL3 locus. METHODS AND RESULTS: In the KAROLA prospective cohort study, 1206 participants of inpatient cardiovascular rehabilitation programmes after experiencing an acute coronary syndrome, myocardial infarction, or coronary intervention were recruited in two clinics in Germany. Active follow-up was conducted over 8 years. Methylation at loci in F2RL3 was characterized by Sequenom matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations of methylation and smoking with secondary cardiovascular events, and cause-specific and all-cause mortality were examined by multiple Cox's regression estimating confounder-controlled hazard ratios. A total of 49 non-fatal myocardial infarctions, 41 non-fatal strokes, 64 cardiovascular deaths, and 50 deaths due to other causes were observed. In Cox's models controlling for established prognostic factors, F2RL3 methylation was strongly associated with mortality. Adjusted hazard ratios (95% confidence intervals) for death from cardiovascular, non-cardiovascular, or any cause were 2.32 (0.97-5.58), 5.16 (1.81-14.7), and 3.19 (1.64-6.21) in subjects in the lowest quartile of methylation in comparison to the highest quartile. In contrast, no association was seen with the combined secondary event outcome. The strong association of smoking with all outcomes was markedly attenuated when F2RL3 was included in the regression models. CONCLUSION: The results seem to indicate methylation in F2RL3 to be a potential mediator of the detrimental impact of smoking and to be strongly related to mortality among patients with stable coronary heart disease. Multidisciplinary research efforts are needed to unravel prognostic, preventive, and therapeutic potentials of these pronounced associations.
AIMS: In a recent genome-wide study, cytosine bases in the F2RL3 gene, which codes for a protein relevant for cardiovascular physiology, were discovered to be hypomethylated in smokers. We aimed to determine the clinical importance of methylation at the F2RL3 locus. METHODS AND RESULTS: In the KAROLA prospective cohort study, 1206 participants of inpatient cardiovascular rehabilitation programmes after experiencing an acute coronary syndrome, myocardial infarction, or coronary intervention were recruited in two clinics in Germany. Active follow-up was conducted over 8 years. Methylation at loci in F2RL3 was characterized by Sequenom matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations of methylation and smoking with secondary cardiovascular events, and cause-specific and all-cause mortality were examined by multiple Cox's regression estimating confounder-controlled hazard ratios. A total of 49 non-fatal myocardial infarctions, 41 non-fatal strokes, 64 cardiovascular deaths, and 50 deaths due to other causes were observed. In Cox's models controlling for established prognostic factors, F2RL3 methylation was strongly associated with mortality. Adjusted hazard ratios (95% confidence intervals) for death from cardiovascular, non-cardiovascular, or any cause were 2.32 (0.97-5.58), 5.16 (1.81-14.7), and 3.19 (1.64-6.21) in subjects in the lowest quartile of methylation in comparison to the highest quartile. In contrast, no association was seen with the combined secondary event outcome. The strong association of smoking with all outcomes was markedly attenuated when F2RL3 was included in the regression models. CONCLUSION: The results seem to indicate methylation in F2RL3 to be a potential mediator of the detrimental impact of smoking and to be strongly related to mortality among patients with stable coronary heart disease. Multidisciplinary research efforts are needed to unravel prognostic, preventive, and therapeutic potentials of these pronounced associations.
Authors: Weiliang Qiu; Emily Wan; Jarrett Morrow; Michael H Cho; James D Crapo; Edwin K Silverman; Dawn L DeMeo Journal: Epigenetics Date: 2015 Impact factor: 4.528
Authors: Yan V Sun; Alicia K Smith; Karen N Conneely; Qiuzhi Chang; Weiyan Li; Alicia Lazarus; Jennifer A Smith; Lynn M Almli; Elisabeth B Binder; Torsten Klengel; Dorthie Cross; Stephen T Turner; Kerry J Ressler; Sharon L R Kardia Journal: Hum Genet Date: 2013-05-09 Impact factor: 4.132
Authors: Jiaxuan Liu; Wei Zhao; Farah Ammous; Stephen T Turner; Thomas H Mosley; Xiang Zhou; Jennifer A Smith Journal: Epigenetics Date: 2019-03-14 Impact factor: 4.528
Authors: Yan Zhang; Rongxi Yang; Barbara Burwinkel; Lutz P Breitling; Bernd Holleczek; Ben Schöttker; Hermann Brenner Journal: Int J Epidemiol Date: 2014-02-07 Impact factor: 7.196