Genetics of the metabolic Syndrome

PIROLA CJ

Miami, FL, USA

Conferencia; XVII scientific meeting of the InterAmerican Society of Hypertension,.; 2007

InterAmerican Society of Hypertension,.

GENETICS OF METABOLIC SYNDROME   Carlos J Pirola, PhD, FAHA. Cardiologìa Molecular. Instituto de Investigaciones Mèdicas A Lanari. Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.   Although there is a debate surrounding the concept of metabolic syndrome (MS), five screening variables used to identified individuals with MS are waist circumference, circulanting levels of triacylglycerols and high density lipoprotein cholesterol (HDL), fasting glucose and blood pressure of which different cut-offs have been proposed. Nevertheless, MS is recognized as a major and prevalent cardiovascular and type 2 diabetes risk factor by bodies such as WHO, NCEP-ATPIII and IDF. Although the definition of the phenotype is imprecise, MS includes a contellation of complex diseases such as type 2 diabetes (T2D), dislipidemias, central obesity and hypertension. Not to mention the proimmflamatory and prothrombotic state, ovarian polychistosis and hepatic esteatosis. The genetics of each of these diseases is complex by itself and vary in a spectrum from monogenic and syndromic forms, usually rare, to the most common polygenic and multifactorial form. Indeed patients with certain rare single gene disorders, such as mutation of MC4R and PPARg, express clusters of abnormalities seen in MS. In addition, studies in human using the candidate gene or genome wide scan approach indicate that common genetic variants of genes such as TNFa, ADRB3, SLC6A4, INSIG2, GAD2, CLOCK, etc are associated with the development of MS. Lack of replication of findings may be due to the roles of gene-gene and gene-environment interactions, ethnicity/race and sex. Genome wide scan have also provided several chromosomal regions associated with some of the components of MS. In addition, animals models through comparative genomics can give a map for candidate loci in human. For instance, recently Stoll et al. have found 26 chromosomal regions in the human genome that are likely to harbor hypertension genes. Taken together several thousands of putative genes emerged from these studies. One promising approch is to narrow the list by using bioinformatic tools for prioritization. For example, recently, Elbers et al. reported that by analysing five susceptibility loci for T2D and obesity encompassing a total of 612 genes 27 functional genes involved in eating behaviour, metabolism and immflamation have been pinpointed using six free available bioinformatic tools. As with most complex diseases, it is premature to propose molecular genetic testing for diagnosis (at least for the polygenic and multifactorial forms) and treatment. However, the involvement in the development of MS of genes such as SLC6A4, PPARa and PPARg  whose products are already the targets for approved drugs may suggest new avenues for MS pharmacological treatment.