Research Article Details
| Article ID: | A48377 |
| PMID: | 14506613 |
| Source: | Metabolism |
| Title: | Aldehyde dehydrogenase 2 and beta3-adrenergic receptor gene polymorphisms: their association with elevated liver enzymes and metabolic syndrome. |
| Abstract: | Recent studies indicate that some patients with nonalcoholic fatty liver have ongoing liver injury that may progress from steatosis to steatohepatitis or fibrosis. The present study was designed to clarify the clinical features of liver dysfunction observed in the course of workplace physical check-ups in relation to multiple risk factor syndrome including obesity, hyperlipidemia, hypertension, and impaired glucose tolerance, and to clarify the involvement of aldehyde dehydrogenase 2 (ALDH2) and beta(3)-adrenergic receptor (beta3-AR) gene polymorphisms in elevation of liver enzymes. One hundred forty-eight male workers 35 years of age were enrolled. They were requested to answer questionnaires about drinking and smoking habits, and underwent urinalysis, physical and peripheral blood examinations, blood chemistry, electrocardiogram and chest x-rays. The genotypes of ALDH2 and beta3-AR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subjects were divided into active ALDH2 or inactive ALDH2 groups. They were also divided into 2 groups according to the beta3-AR genotype. The relationships between ALDH2 and beta3-AR gene polymorphism and the results of the physical examination including liver function tests were analyzed. The subjects were also divided according to the number of components of metabolic syndrome. The prevalence of elevated alanine aminotransferase (ALT) level increased with the accumulation of components of metabolic syndrome. Active ALDH2 was associated with elevated ALT level to a greater degree than beta3-AR polymorphism. Among those with normal body mass index (BMI), the genotypes of ALDH2 and beta3-AR were strongly associated with elevated ALT level. Logistic regression analysis revealed that BMI, triglyceride level, and ALDH2 genotype were associated with ALT elevation. In conclusion, evaluating the genotype of ALDH2 and beta3-AR may assist in predicting and preventing the development of fatty liver which may be related to multiple risk factor syndrome. |
| DOI: | 10.1016/s0026-0495(03)00183-5 |
| 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |