Research Article Details
| Article ID: | A20647 |
| PMID: | 25835554 |
| Source: | Int J Obes (Lond) |
| Title: | Heme oxygenase-1 gene promoter polymorphism and the risk of pediatric nonalcoholic fatty liver disease. |
| Abstract: | BACKGROUND AND OBJECTIVES: Oxidative stress and the insulin-resistant state are thought to be key components in the pathogenesis of pediatric nonalcoholic fatty liver disease (NAFLD). Heme oxygenase (HO) is important in the defense against oxidative stress. This study aimed to assess the association of HO-1 gene promoter polymorphism and insulin resistance with NAFLD among obese children. METHODS: A total of 101 obese children aged 6-17 years were recruited. Anthropometric, serum biochemical variables and biomarkers for glucose and insulin metabolism were measured. We screened the allelic frequencies of (GT)n repeats in the HO-1 gene promoter among these obese children. NAFLD was determined through liver ultrasonography. Because the distribution of numbers of (GT)n repeats was bimodal, we divided the alleles into two classes: class S included shorter (27) repeats, and class L included longer (⩾27) repeats. We assessed the effects of the length of (GT)n repeats in HO-1 gene promoter on pediatric NAFLD. RESULTS: Of the 101 obese subjects, 27 (26.7%) had NAFLD. The alanine aminotransferase level was higher in patients carrying L alleles (L/L and L/S) than patients with S alleles (S/S) (46.2±49.3 IU|(-1) versus 30.2±20.1 IU|(-1); P=0.027). The significant risk factors for pediatric NAFLD were patients carrying L alleles (L/L and L/S) (odds ratio (OR)=18.84; 95% confidence interval (CI): 1.45-245.22; P=0.025), homeostasis model assessment of insulin resistance (OR=1.40; 95% CI: 1.07-1.83; P=0.014) and age (OR=1.24; 95% CI: 1.03-1.50; P=0.025). CONCLUSION: In this hospital-based study, the obese children with longer GT repeats in the HO-1 gene promoter and insulin resistance were susceptible to NAFLD. |
| DOI: | 10.1038/ijo.2015.46 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 | |
|---|---|---|---|---|---|---|---|
| D482 | Heme Oxygenase | Biological drug | -- | -- | -- | Under clinical trials | Details |
| 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 |
| 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 |