Research Article Details
| Article ID: | A31600 |
| PMID: | 30218427 |
| Source: | Dig Dis Sci |
| Title: | PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals. |
| Abstract: | BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing 3 (PNPLA3) gene has been associated with the development of alcoholic and nonalcoholic steatohepatitis. Using a newly developed and validated assay for PNPLA3, we explored the prevalence of gene polymorphisms in a cohort of HCV/HIV-coinfected individuals to determine whether there was an association with insulin resistance or hepatic fibrosis. METHODS: A high-resolution melting point (HRM) assay was developed and validated. The assay was used to evaluate samples obtained in the context of a clinical trial performed at ACTG sites across the USA in HIV-infected patients. Clinical features and treatment outcomes were assessed in relation to the PNPLA3 genotype. RESULTS: The HRM methodology demonstrated 100% concordance with results obtained by Sanger sequencing. Among 241 participants tested, 66.0% had the wild-type allele (CC) and the remainder had the aberrant PNPLA3 gene polymorphism in the homozygotic (GG) or heterozygotic (CG) form. Race and ethnicity were associated with PNPLA3 genotype but fibrosis stage, Homeostatic Model Assessment of Insulin Resistance, and HCV treatment outcome were not. CONCLUSION: The HRM method is an effective, rapid technique for characterizing PNPLA3 genotype. In those with HCV/HIV infection, nearly 40% carry gene polymorphisms associated with the development of NASH or ASH. Prospective studies should focus on this group to determine whether they represent a subset of HIV-infected persons at increased risk of fibrotic progression. |
| DOI: | 10.1007/s10620-018-5278-y |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| 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 | |
|---|---|---|---|---|---|
| I09 | 104 | Bacterial infectious disease | A disease by infectious agent that results_in infection, has_material_basis_in Bacteria. http://en.wikipedia.org/wiki/Pathogenic_bacteria | disease by infectious agent | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |