Gene–Environment Interactions and Susceptibility to Metabolic Syndrome and Other Chronic Diseases

Abstract

There is an intrinsic complexity in the pathogenesis of common diseases. The concept of gene-environment interaction is receiving support from emerging evidence coming primarily from studies involving diet and cardiovascular disease (CVD) and its various risk factors. The accumulating evidence shows that common variants at candidate genes for lipid metabolism, inflammation, and obesity are associated with altered plasma levels of classic and new biomarkers of metabolic syndrome and CVD risk. Major contributors to this knowledge have been a series of large population studies containing phenotype-rich databases and dietary information to which genetic data have been added. Although this approach has provided strong evidence supporting the concept of gene-diet interactions modulating CVD risk factors, the strength of the individual effect is very small, and the replication among studies is rather disappointing. Current population studies are starting to incorporate experimental and analytical approaches that could provide more solid and comprehensive results. However, other limitations, such as the size of the populations required to examine higher-level interactions, are still major obstacles to translating this knowledge into practical public health applications. Nevertheless, data from numerous molecular and genetic epidemiological studies provide tantalizing evidence suggesting that gene-environment interactions, i.e., the modulation by a genetic polymorphism of a dietary component effect on a specific phenotype (e.g., cholesterol levels and obesity), can interact in ways that increase the risk for developing chronic disease, including susceptibility to developing the metabolic syndrome. Once further experience is gained from patients and/or individuals at high risk, more personalized genetic-based approaches may be applied toward the primary prevention and treatment of CVDs and other complex inflammatory diseases.