Genetic alteration may represent early stage of smoking-induced cardiovascular damage
A new study uncovers a previously unrecognized link between tobacco smoking and a gene known to influence the cardiovascular system, possibly identifying an early stage of smoking-associated cardiovascular pathology. The research, published by Cell Press in the April issue of the American Journal of Human Genetics, may serve to guide future research strategies aimed at identifying and counteracting mechanisms of smoking-induced pathology.
Tobacco smoking is powerfully addictive and damages the pulmonary and cardiovascular systems, leading to malignancy and premature death. “Although the promotion of smoking cessation clearly remains imperative, a better understanding of the pathophysiological processes linking tobacco smoking and its sequelae could yield opportunities to positively influence disease risk in the large population of continuing smokers,” explains lead study author, Dr. Lutz P. Breitling from the German Cancer Research Center in Heidelberg, Germany.
One possible mechanism that has the potential for mediating the harmful effects of tobacco smoking is DNA methylation. DNA methylation, the attachment of methyl groups to specific sites within a section of DNA, is recognized as an important mechanism for regulating gene function and may play a significant role in diseases with a complex phenotype. Although previous studies have linked nicotine and smoking with altered methylation of several cancer-related genes, comparison of methylation status between heavy smokers who do not have cancer and individuals who have never smoked has not been fully examined.
Dr. Breitling and colleagues used a recently developed genetic screening technique to conduct a genome-wide search for differential methylation correlated with tobacco smoking in 177 current, former and never smokers. The researchers discovered a single section of DNA that exhibited lower methylation in smokers. The site was located within a gene called coagulation factor II receptor-like 3 gene (F2RL3). F2RL3 has been linked with the process of blood clotting and with other cardiovascular functions. Interestingly, the protein coded by this gene has never been mentioned in the smoking literature.
“Our results show that the gene coding for a potential drug target of cardiovascular importance features altered methylation patterns in smokers,” concludes Dr. Breitling. “Intriguing perspectives lie in the possibility that this gene could be causally involved at a very initial stage of smoking-related cardiovascular pathology. A better understanding of its role might open up avenues for preventing the development of associated disease in subjects unable to quit smoking.”
Lutz P Breitling, Rongxi Yang, Bernhard Korn, Barbara Burwinkel und Hermann Brenner:Tobacco smoking-related differential DNA methylation: 27k discovery and replication. American Journal of Human Genetics 2011, DOI: 10.1016/j.ajhg.2011.03.003
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.