Current Genetics and Epigenetics of Smoking/Tobacco-Related Cardiovascular Disease

Abstract

Abstract-Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns. This could render the genetics and epigenetics of smoking-related cardiovascular disease a textbook example of environmental epigenetics and modern approaches to multimodal data analysis. A pronounced association of smoking-related methylation patterns in the F2RL3 gene with prognosis in patients with stable coronary heart disease has recently been described. Nonetheless, surprisingly little concrete knowledge on the role of specific genetic variants and epigenetic modifications in the development of cardiovascular diseases in people who smoke has been accumulated. Beyond the current knowledge, the present review briefly outlines some chief challenges and priorities for moving forward in this field. variation in antioxidative resilience seems to have no clinical cardiovascular consequences by itself, but-in interaction with the excessive oxidative stress caused by smoking-it means that smoking-associated cardiovascular risks are much greater in ε4 carriers than in other subjects. 10 It has been realized that such gene-environment interactions could also interfere with the performance of lipid-lowering drugs, but the extent of this potentially far-reaching problem still needs to be clarified. 11Given the multitude of physiological phenomena involved in tobacco-smoking-related cardiovascular disease (ref. 12 for an informative overview), it is hardly surprising that similar interactions with smoking have been reported for sequence variants in candidate genes coding for proteins as diverse as lipoprotein lipase and interleukin-6, 10 prothrombotic mutations like factor II G20210A, 13 or transforming growth factor-β1.14 One study investigating an interaction of interleukin-18 polymorphisms with smoking regarding cardiovascular disease risk was exceptional for its laudable collaborative design emphasizing statistical power.15 Nonetheless, the level of evidence for the vast majority of currently suggested gene-smoking interactions ultimately remains very limited. The evolution of findings concerning an interaction between tobacco-smoking and variants in glutathione S-transferase genes with respect to cardiovascular disease risk-which started out as a seemingly plausible effect modification supported by multiple lines of evidence 8 and was further sugested later meta-analysis, 16 only to vanish with subsequent sample size escalation 17 -should be taken as a reminder of the danger of prematurely overinterpreting gene-smoking interactions or even higher order interactions (eg, gene-age-smoking). 18Thorough replication and follow-up studies need to become more of a norm in this statistically challenging field. A New Era of EpigeneticsStudies on epigenetic aspects of health and disease have exploded in recent years, mainly because of technological a...

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