Current Data and New Insights into the Genetic Factors of Atherogenic Dyslipidemia Associated with Metabolic Syndrome.

Abstract

Atherogenic dyslipidemia plays a critical role in the development of metabolic syndrome (MetS), being one of its major components, along with central obesity, insulin resistance, and hypertension. In recent years, the development of molecular genetics techniques and extended analysis at the genome or exome level has led to important progress in the identification of genetic factors (heritability) involved in lipid metabolism disorders associated with MetS. In this review, we have proposed to present the current knowledge related to the genetic etiology of atherogenic dyslipidemia, but also possible challenges for future studies. Data from the literature provided by candidate gene-based association studies or extended studies, such as genome-wide association studies (GWAS) and whole exome sequencing (WES,) have revealed that atherogenic dyslipidemia presents a marked genetic heterogeneity (monogenic or complex, multifactorial). Despite sustained efforts, many of the genetic factors still remain unidentified (missing heritability). In the future, the identification of new genes and the molecular mechanisms by which they intervene in lipid disorders will allow the development of innovative therapies that act on specific targets. In addition, the use of polygenic risk scores (PRS) or specific biomarkers to identify individuals at increased risk of atherogenic dyslipidemia and/or other components of MetS will allow effective preventive measures and personalized therapy.