The metabolic syndrome: a crossroad for genotype-phenotype associations in atherosclerosis

The metabolic syndrome comprises a set of metabolic and physiologic risk factors associated with elevated cardiovascular disease risk. The expression of each one of its major factors (hypertriglyceridemia, low high-density lipoprotein cholesterol levels, hypertension, abdominal obesity, and insulin resistance) has been found to be the result of complex interactions between genetic and environmental factors. Moreover, obesity may play a major role in triggering the metabolic syndrome by interacting with genetic variants at candidate genes for dyslipidemia, hypertension, and insulin resistance. In support of this hypothesis, several studies at multiple candidate genes have already demonstrated the significance of these interactions; however, the data and their reliability are still very limited, and in many cases replication studies are still lacking in the literature. Therefore, more studies with better epidemiologic design and standardized adiposity measures are needed to estimate the contribution of body weight and fat distribution to the genetic predisposition to the metabolic syndrome, which is the most common cardiovascular disease risk factor in industrialized societies.