Research Article Details
| Article ID: | A02918 |
| PMID: | 34199237 |
| Source: | Diagnostics (Basel) |
| Title: | Three Different Genetic Risk Scores Based on Fatty Liver Index, Magnetic Resonance Imaging and Lipidomic for a Nutrigenetic Personalized Management of NAFLD: The Fatty Liver in Obesity Study. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. The pathogenesis of NAFLD is complex; available data reveal that genetics and ascribed interactions with environmental factors may play an important role in the development of this morbid condition. The purpose of this investigation was to assess genetic and non-genetic determinants putatively involved in the onset and progression of NAFLD after a 6-month weight loss nutritional treatment. A group of 86 overweight/obese subjects with NAFLD from the Fatty Liver in Obesity (FLiO) study were enrolled and metabolically evaluated at baseline and after 6 months. A pre-designed panel of 95 genetic variants related to obesity and weight loss was applied and analyzed. Three genetic risk scores (GRS) concerning the improvement on hepatic health evaluated by minimally invasive methods such as the fatty liver index (FLI) (GRSFLI), lipidomic-OWLiver®-test (GRSOWL) and magnetic resonance imaging (MRI) (GRSMRI), were derived by adding the risk alleles genotypes. Body composition, liver injury-related markers and dietary intake were also monitored. Overall, 23 SNPs were independently associated with the change in FLI, 16 SNPs with OWLiver®-test and 8 SNPs with MRI, which were specific for every diagnosis tool. After adjusting for gender, age and other related predictors (insulin resistance, inflammatory biomarkers and dietary intake at baseline) the calculated GRSFLI, GRSOWL and GRSMRI were major contributors of the improvement in hepatic status. Thus, fitted linear regression models showed a variance of 53% (adj. R2 = 0.53) in hepatic functionality (FLI), 16% (adj. R2 = 0.16) in lipidomic metabolism (OWLiver®-test) and 34% (adj. R2 = 0.34) in liver fat content (MRI). These results demonstrate that three different genetic scores can be useful for the personalized management of NAFLD, whose treatment must rely on specific dietary recommendations guided by the measurement of specific genetic biomarkers. |
| DOI: | 10.3390/diagnostics11061083 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |