Research Article Details
| Article ID: | A52401 |
| PMID: | 27615511 |
| Source: | Immunobiology |
| Title: | Association of the I148M/PNPLA3 (rs738409) polymorphism with premature coronary artery disease, fatty liver, and insulin resistance in type 2 diabetic patients and healthy controls. The GEA study. |
| Abstract: | The aim of this study was to evaluate the potential use of the I148M/PNPLA3 (rs738409) gene polymorphism as a susceptibility marker for premature coronary artery disease (pCAD) and/or cardiovascular risk factors in Mexican type 2 diabetes mellitus patients (T2DM). The polymorphism was genotyped by 5' exonuclease TaqMan assays in a group of 2572 subjects (1103 with pCAD and 1469 healthy controls) belonging to the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Anthropometric and biochemical measurements were performed in all individuals. The association between the I148M/PNPLA3 (rs738409) gene polymorphism with pCAD and other metabolic and cardiovascular risk factors was evaluated using logistic regression analysis under different statistical approaches including dominant, recessive, heterozygous, additive, and co-dominant models. The polymorphism was not associated with pCAD in the whole group of participants, however, when patients and controls were divided into those with and without T2DM, under additive model, the polymorphism was associated with the presence of pCAD only in patients with T2DM (OR=1.20, 95% CI: 1.01-1.42, Padd=0.042). On the other hand, under several models adjusted for age, gender, body mass index and T2DM, the polymorphism was associated with increased risk of fatty liver and elevated levels of alanine transaminase (ALT) in the whole group of pCAD patients and controls. In the control group, the polymorphism was associated with insulin resistance and coronary artery calcification (CAC) score≥10 under several models. The results suggest that the I148M/PNPLA3 (rs738409) polymorphism is associated with the presence of pCAD in T2DM patients and with some cardiometabolic parameters. The association detected with CAC in the control group indicates that this polymorphism could be a marker for subclinical atherosclerosis. |
| DOI: | 10.1016/j.imbio.2016.08.008 |
| 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 |
| 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 |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | 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 |