Research Article Details
| Article ID: | A05683 |
| PMID: | 33160101 |
| Source: | Mol Metab |
| Title: | Genetic and epigenetic factors determining NAFLD risk. |
| Abstract: | BACKGROUND: Hepatic steatosis is a common chronic liver disease that can progress into more severe stages of NAFLD or promote the development of life-threatening secondary diseases for some of those affected. These include the liver itself (nonalcoholic steatohepatitis or NASH; fibrosis and cirrhosis, and hepatocellular carcinoma) or other organs such as the vessels and the heart (cardiovascular disease) or the islets of Langerhans (type 2 diabetes). In addition to elevated caloric intake and a sedentary lifestyle, genetic and epigenetic predisposition contribute to the development of NAFLD and the secondary diseases. SCOPE OF REVIEW: We present data from genome-wide association studies (GWAS) and functional studies in rodents which describe polymorphisms identified in genes relevant for the disease as well as changes caused by altered DNA methylation and gene regulation via specific miRNAs. The review also provides information on the current status of the use of genetic and epigenetic factors as risk markers. MAJOR CONCLUSION: With our overview we provide an insight into the genetic and epigenetic landscape of NAFLD and argue about the applicability of currently defined risk scores for risk stratification and conclude that further efforts are needed to make the scores more usable and meaningful. |
| DOI: | 10.1016/j.molmet.2020.101111 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |