| Title: | Investigation of Clinical and Genetic phenotypes associated to low and high lipid levels |
| Lead Institution: | University of Palermo |
| Principal investigator: |
Application 205197
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
About
The aim of this study is to interrogate UK Biobank database, by extracting panels of gene variants GWAS (single nucleotide polymorphisms), exomes (rare genetic variants), and try to correlate them with clinical and laboratory phenotypes (including imaging) to understand the genetic architecture of the most common cardio-metabolic diseases, such as cerebro-cardiovascular diseases, liver steatosis, diabetes, cancer, diabetes, cognitive syndromes. The scientific rationale is based on the results of different studies demonstrating that a group of genes, are responsible for several lipid genetic disorders may also affect many clinical phenotypes that are very common in the population such as all the cerebro-cardio-metabolic phenotypes. These genes are responsible of low and high cholesterol diseases that include: i. Familial hypobetalipoproteinemia (FHBL) characterized by apoB and LDL-C levels below the 5th percentile; ii. Abetalipoproteinemia (ABL) characterized by the absence of apoB production in liver and intestine; iii. Chylomicron retention disease characterized by the absence of apoB48 production in the intestine; iv. Familial Hypercholesterolemia due to LDLR, PCSK9, APOB, LDLRAP1 gene mutations; v. Primary hypercholesterolemias due to APOE, ABCG5/8 and LIPA gene mutations; vi. Polygenic hypercholesterolemias due to a high polygenic burden. The cerebro-cardio-metabolic phenotypes typically associated to these rare genetic diseases are the same commonly prevalent in the general population. Taken together, these studies support the possibility that other todate unknown genes may contribute to the genetic architecture of many common chronic diseases. The initial estimate of the project duration is 12 months, unless additional data will be required. The identification of novel genetic patways as a possible determinant of cerebro-cardio-metabolic diseases might open the field for novel therapeutic strategies in the treatment of such conditions. In recent times many companies have developed therapeutic strategies based on genetic results and, if the present study will confirm that one ore more of the above mentioned conditions are associated with genetic pathways, such novel pharmacological targets might represent a future therapeutic option able to correct one or more cerebro-cardio-metabolic diseases.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 16704 | Clinical and Biochemical Characterization of Fabry Disease Associated GLA Gene Variants: Data From a Large Cohort of 469 Thousand Genotyped Subjects of the UK Biobank Database | Antonina Giammanco (+7) | 2025 | Journal of Inherited Metabolic Disease |
Enabling scientific discoveries that improve human health