cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2015-6-73-77cardiovascular-286Research ArticleРАЗНОЕВЛИЯНИЕ КУРЕНИЯ НА СТАТУС МЕТИЛИРОВАНИЯ ДЕЗОКСИРИБОНУКЛЕИНОВОЙ КИСЛОТЫINFLUENCE OF SMOKING ON THE METHYLIZING STATUS OF DESOXYRIBONUCLEIC ACIDКиселеваА. В.KiselevaA. V.

к.б.н., н.с. лаборатории

ЖариковаА. А.ZharikovaA. A.

м.н.с. лаборатории

МешковА. Н.MeshkovA. N.

к.м.н., руководитель лаборатории молекулярной генетики

meshkov@lipidclinic.ruФГБУ “Государственный научно-исследовательский центр профилактической медицины” Минздрава России, МоскваРоссияNational Research Center for Preventive Medicine of the Ministry of Health, MoscowRussian Federation2015201220151467377Copyright © Киселева А.В., Жарикова А.А., Мешков А.Н., 20152015Киселева А.В., Жарикова А.А., Мешков А.Н.Kiseleva A.V., Zharikova A.A., Meshkov A.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/286

Курение один из главных факторов риска многих заболеваний, таких как ишемическая болезнь сердца, инсульт, хроническая обструктивная болезнь легких. Знание механизмов, через которые курение влияет на развитие этих заболеваний, может помочь найти новые способы профилактики и лечения. Исследования последних лет показали влияние курения на эпигенетические механизмы наследования, в частности на статус метилирования дезоксирибонуклеиновой кислоты (ДНК). Данный обзор посвящен анализу влияния курения на метилирование ДНК. В литературе описаны >60 генов, уровень метилирования которых достоверно ассоциирован с курением. Выявлена связь уровня метилирования генов AHRR, MMP25, PTGDS, WWC3, SASH1 не только с курением, но и с атеросклерозом. 

Smoking is one of the main factors of a wide range of diseases as ischemic heart disease, stroke, chronic obstructive pulmonary disease. To know mechanisms of smoking influence on the course of these diseases might lead to discovery of novel methods of diagnostics and prevention. Recent studies showed the impact of smoking on epigenetic mechanisms of heredity, particularly on the status of DNA methylizing. Current review focuses on the analysis of smoking influence of DNA methylizing. There are >60 genes described, methylizing of which is related to smoking. There is relation of methylizing level of genes AHRR, MMP25, PTGDS, WWC3, SASH1 not only with smoking but atherosclerosis. 

курениеметилированиеEWASэпигенетикаsmokingmethylizingEWASepigeneticsReferencesBreitling LP. Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. Arterioscler Thromb Vasc Biol 2013; 33: 1468-72.Breitling LP. Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. Arterioscler Thromb Vasc Biol 2013; 33: 1468-72.Conen D, Everett BM, Kurth T, et al. Smoking, smoking status, and risk for symptomatic peripheral artery disease in women: a cohort study. Ann Intern Med 2011; 154: 719-26.Conen D, Everett BM, Kurth T, et al. Smoking, smoking status, and risk for symptomatic peripheral artery disease in women: a cohort study. Ann Intern Med 2011; 154: 719-26.Louhelainen N, Stark H, Mazur W, et al. Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study. BMC Pulm Med 2010; 10:13.Louhelainen N, Stark H, Mazur W, et al. Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study. BMC Pulm Med 2010; 10:13.Bouloukaki I, Tsiligianni IG, Tsoumakidou M, et al. Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation. BMC Pulm Med 2011; 11: 35.Bouloukaki I, Tsiligianni IG, Tsoumakidou M, et al. Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation. BMC Pulm Med 2011; 11: 35.Vineis P, Alavanja M, Buffler P, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 2004; 96: 99-106.Vineis P, Alavanja M, Buffler P, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 2004; 96: 99-106.Luo J, Margolis KL, Wactawski-Wende J, et al. Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. BMJ 2011; 342: d1016.Luo J, Margolis KL, Wactawski-Wende J, et al. Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. BMJ 2011; 342: d1016.Wan ES, Qiu W, Baccarelli A, et al. Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome. Hum Mol Genet 2012; 21(13): 3073-82.Wan ES, Qiu W, Baccarelli A, et al. Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome. Hum Mol Genet 2012; 21(13): 3073-82.Breitling LP, Yang R, Korn B, et al. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Hum Genet 2011; 88(4): 450-7.Breitling LP, Yang R, Korn B, et al. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Hum Genet 2011; 88(4): 450-7.Shenker NS, Polidoro S, van Veldhoven K, et al. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet 2013; 22(5): 843-51.Shenker NS, Polidoro S, van Veldhoven K, et al. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet 2013; 22(5): 843-51.Zeilinger S, Kühnel B, Klopp N, et al. Tobacco smoking leads to extensive genome￾wide changes in DNA methylation. PLoS One 2013; 8(5): e63812.Zeilinger S, Kühnel B, Klopp N, et al. Tobacco smoking leads to extensive genome￾wide changes in DNA methylation. PLoS One 2013; 8(5): e63812.Sun YV, Smith AK, Conneely KN, et al. Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans. Hum Genet 2013; 132(9):1027-37.Sun YV, Smith AK, Conneely KN, et al. Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans. Hum Genet 2013; 132(9):1027-37.Dogan MV, Shields B, Cutrona C, et al. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics. 2014; 15: 151.Dogan MV, Shields B, Cutrona C, et al. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics. 2014; 15: 151.Tsaprouni LG, Yang TP, Bell J, et al. Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics 2014; 9(10): 1382-96.Tsaprouni LG, Yang TP, Bell J, et al. Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics 2014; 9(10): 1382-96.Bauer M, Linsel G, Fink B, et al. A varying T cell subtype explains apparent tobacco smoking induced single CpG hypomethylation in whole blood. Clin Epigenetics 2015; 7(1): 81.Bauer M, Linsel G, Fink B, et al. A varying T cell subtype explains apparent tobacco smoking induced single CpG hypomethylation in whole blood. Clin Epigenetics 2015; 7(1): 81.Zeller T, Wild P, Szymczak S, et al. Genetics and beyond–the transcriptome of human monocytes and disease susceptibility. PLoS ONE 2010; 5(5): e10693.Zeller T, Wild P, Szymczak S, et al. Genetics and beyond–the transcriptome of human monocytes and disease susceptibility. PLoS ONE 2010; 5(5): e10693.Reynolds LM, Wan M, Ding J, et al. 2015, DNA Methylation of the Aryl Hydrocarbon Receptor Repressor Associations with Cigarette Smoking and Subclinical Atherosclerosis. Circ Cardiovasc Genet 2015; pii:CIRCGENETICS.115.001097.Reynolds LM, Wan M, Ding J, et al. 2015, DNA Methylation of the Aryl Hydrocarbon Receptor Repressor Associations with Cigarette Smoking and Subclinical Atherosclerosis. Circ Cardiovasc Genet 2015; pii:CIRCGENETICS.115.001097.Weidmann H, Touat-Hamici Z, Durand H, et al. SASH1, a new potential link between smoking and atherosclerosis. Atherosclerosis 2015; 242(2): 571-9.Weidmann H, Touat-Hamici Z, Durand H, et al. SASH1, a new potential link between smoking and atherosclerosis. Atherosclerosis 2015; 242(2): 571-9.Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009; 462: 315-22.Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009; 462: 315-22.Soma T, Kaganoi J, Kawabe A, et al. Nicotine induces the fragile histidine triad methylation in human esophageal squamous epithelial cells. Int J Cancer 2006; 119(5): 1023-7.Soma T, Kaganoi J, Kawabe A, et al. Nicotine induces the fragile histidine triad methylation in human esophageal squamous epithelial cells. Int J Cancer 2006; 119(5): 1023-7.Liu Y, Lan Q, Siegfried JM, et al. Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia 2006; 8: 46-51.Liu Y, Lan Q, Siegfried JM, et al. Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia 2006; 8: 46-51.Kaur J, Demokan S, Tripathi SC, et al. Promoter hypermethylation in Indian primary oral squamous cell carcinoma. Int J Cancer 2010; 127(10): 2367-73.Kaur J, Demokan S, Tripathi SC, et al. Promoter hypermethylation in Indian primary oral squamous cell carcinoma. Int J Cancer 2010; 127(10): 2367-73.Hsiung DT, Marsit CJ, Houseman EA, et al. Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2007; 16(1): 108-14;Hsiung DT, Marsit CJ, Houseman EA, et al. Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2007; 16(1): 108-14;Accomando WP, Wiencke JK, Houseman EA, et al. Quantitative reconstruction of leukocyte subsets using DNA methylation. Genome Biol 2014; 15(3): R50.Accomando WP, Wiencke JK, Houseman EA, et al. Quantitative reconstruction of leukocyte subsets using DNA methylation. Genome Biol 2014; 15(3): R50.Reinius LE, Acevedo N, Joerink M, et al. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS One 2012; 7(7): e41361.Reinius LE, Acevedo N, Joerink M, et al. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS One 2012; 7(7): e41361.Joubert BR, Håberg SE, Nilsen RM, et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect 2012; 120: 1425-31.Joubert BR, Håberg SE, Nilsen RM, et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect 2012; 120: 1425-31.Novakovic B, Ryan J, Pereira N, et al. Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy. Epigenetics 2014; 9(3): 377-86.Novakovic B, Ryan J, Pereira N, et al. Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy. Epigenetics 2014; 9(3): 377-86.Monick MM, Beach SR, Plume J, et al. Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers. Am J Med Genet B Neuropsychiatr Genet 2012; 159B(2): 141-51.Monick MM, Beach SR, Plume J, et al. Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers. Am J Med Genet B Neuropsychiatr Genet 2012; 159B(2): 141-51.DAVID https://david.ncifcrf.gov/ (28 September 2015).DAVID https://david.ncifcrf.gov/ (28 September 2015).Sherman BT, Huang da W, Tan Q, et al. DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics 2007; 8: 426.Sherman BT, Huang da W, Tan Q, et al. DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics 2007; 8: 426.Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2: 372-7.Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2: 372-7.Verdugo RA, Zeller T, Rotival M, et al. Graphical Modeling of Gene Expression in Monocytes Suggests Molecular Mechanisms Explaining Increased Atherosclerosis in Smokers. PLoS ONE 2013; 8(1): e50888.Verdugo RA, Zeller T, Rotival M, et al. Graphical Modeling of Gene Expression in Monocytes Suggests Molecular Mechanisms Explaining Increased Atherosclerosis in Smokers. PLoS ONE 2013; 8(1): e50888.Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32(9): 2045-51.Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32(9): 2045-51.Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 2006; 6(7): 508-19.Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 2006; 6(7): 508-19.Redgrave JNE, Lovett JK, Rothwell PM. Histological features of symptomatic carotid plaques in relation to age and smoking: the oxford plaque study. Stroke J Cereb Circ 2010; 41(10): 2288-94.Redgrave JNE, Lovett JK, Rothwell PM. Histological features of symptomatic carotid plaques in relation to age and smoking: the oxford plaque study. Stroke J Cereb Circ 2010; 41(10): 2288-94.McEvoy JW, Blaha MJ, DeFilippis AP, et al. Cigarette smoking and cardiovascular events: role of inflammation and subclinical atherosclerosis from the multiethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 2015; 35(3): 700-9.McEvoy JW, Blaha MJ, DeFilippis AP, et al. Cigarette smoking and cardiovascular events: role of inflammation and subclinical atherosclerosis from the multiethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 2015; 35(3): 700-9.Talhout R, Schulz T, Florek E, et al. Hazardous compounds in tobacco smoke. Int J Environ Res Public Health 2011; 8(2): 613-28.Talhout R, Schulz T, Florek E, et al. Hazardous compounds in tobacco smoke. Int J Environ Res Public Health 2011; 8(2): 613-28.Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 2014; 34(3): 509-15.Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 2014; 34(3): 509-15.Zeller C, Hinzmann B, Seitz S, et al. SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer. Oncogene 2003; 22(19): 2972-83.Zeller C, Hinzmann B, Seitz S, et al. SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer. Oncogene 2003; 22(19): 2972-83.Martini M, Gnann A, Scheikl D, et al. The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion. Int J Biochem Cell Biol 2011; 43(11): 1630-40.Martini M, Gnann A, Scheikl D, et al. The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion. Int J Biochem Cell Biol 2011; 43(11): 1630-40.Rimkus C, Martini M, Friederichs J, et al. Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer. Br J Cancer 2006; 95(10): 1419-23.Rimkus C, Martini M, Friederichs J, et al. Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer. Br J Cancer 2006; 95(10): 1419-23.Chen E, Chen Y, Dong L, et al. Effects of SASH1 on lung cancer cell proliferation, apoptosis, and invasion in vitro. Tumour Biol J Int Soc Oncodevelopmental Biol Med 2012; 33(5): 1393-401.Chen E, Chen Y, Dong L, et al. Effects of SASH1 on lung cancer cell proliferation, apoptosis, and invasion in vitro. Tumour Biol J Int Soc Oncodevelopmental Biol Med 2012; 33(5): 1393-401.Lin S, Zhang J, Xu J, et al. Effects of SASH1 on melanoma cell proliferation and apoptosis in vitro. Mol Med Rep 2012; 6(6): 1243-8.Lin S, Zhang J, Xu J, et al. Effects of SASH1 on melanoma cell proliferation and apoptosis in vitro. Mol Med Rep 2012; 6(6): 1243-8.Dertinger SD, Silverstone AE, Gasiewicz TA. Influence of aromatic hydrocarbon receptor- mediated events on the genotoxicity of cigarette smoke condensate. Carcinogenesis 1998; 19: 2037-42.Dertinger SD, Silverstone AE, Gasiewicz TA. Influence of aromatic hydrocarbon receptor- mediated events on the genotoxicity of cigarette smoke condensate. Carcinogenesis 1998; 19: 2037-42.Savouret JF, Berdeaux A, Casper RF. The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases. Nutr Metab Cardiovasc Dis 2003; 13: 104-13.Savouret JF, Berdeaux A, Casper RF. The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases. Nutr Metab Cardiovasc Dis 2003; 13: 104-13.Kerley-Hamilton JS, Trask HW, Ridley CJ, et al. Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice. Toxicol Sci 2012; 126(2): 391-404.Kerley-Hamilton JS, Trask HW, Ridley CJ, et al. Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice. Toxicol Sci 2012; 126(2): 391-404.Kazantseva MG, Highton J, Stamp LK, et al. Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis. Arthritis Res Ther 2012; 14(5): R208.Kazantseva MG, Highton J, Stamp LK, et al. Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis. Arthritis Res Ther 2012; 14(5): R208.Awji EG, Chand H, Bruse S, et al. Wood Smoke Enhances Cigarette Smoke-Induced Inflammation by Inducing the Aryl Hydrocarbon Receptor Repressor in Airway Epithelial Cells. Am J Respir Cell Mol Biol 2015; 52: 377-86.Awji EG, Chand H, Bruse S, et al. Wood Smoke Enhances Cigarette Smoke-Induced Inflammation by Inducing the Aryl Hydrocarbon Receptor Repressor in Airway Epithelial Cells. Am J Respir Cell Mol Biol 2015; 52: 377-86.

The authors declare that there are no conflicts of interest present.