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Review: Genetics of the cardiometabolic syndrome: new insights and therapeutic implications

Departamento de Sustancias Vasoactivas y Cardiología Molecular, Instituto de Investigaciones A Lanari, Universidad de Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina

Carlos J. Pirola

Departamento de Sustancias Vasoactivas y Cardiología Molecular, Instituto de Investigaciones A Lanari, Universidad de Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina, carlospirola{at}ciudad.com.ar, pirola.carlos@lanari. fmed.uba.ar

Although the definition of the phenotype is imprecise, cardiometabolic syndrome (CMS) includes a constellation of complex diseases such as type 2 diabetes, dislipidemias, central obesity and hypertension, proinflammatory and prothrombotic states, ovarian polycystosis and fatty liver. The genetics of each disease is complex in itself and varies in spectrum from monogenic and syndromic models of inheritance, usually rare, to the most common polygenic and multifactorial forms. In addition, human studies using the candidate-gene approach indicate that common genetic variants of several genes are associated with the development of CMS. Genome-wide scans have also provided several chromosomal regions associated with some of the components of CMS. In addition, through comparative genomics animal models can generate a map for candidate loci in humans and a promising approach is offered by bioinformatic tools for gene prioritization. Lastly, the involvement of genes whose products are already the targets for approved drugs, such as SLC6A4, PPAR and PPAR , in the development of CMS suggests new avenues for CMS pharmacological treatment.

Key Words: cardiometabolic syndrome • metabolic syndrome • insulin resistance • obesity • hypertension • diabetes • genetics • gene • variants.

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