Research Article Details
| Article ID: | A20187 |
| PMID: | 26097608 |
| Source: | Int J Clin Exp Pathol |
| Title: | Interactions of central obesity with rs3918242 on risk of non-alcoholic fat liver disease: a preliminary case-control study. |
| Abstract: | NAFLD is a complex disease characterized by inflammation and insulin resistance which is determined by an interaction of genetics and environmental factors. MMP gene has been implicated in relation to inflammation and insulin resistance. The preliminary case-control study aimed to investigate the association between Matrix metalloproteinase (MMP)-9-1562C/T (rs3918242), MMP-2-1306C/T (rs243865) and risk of NAFLD and to further evaluate the interactions of central obesity with rs3918242 and rs243865. Two variants, rs3918242 and rs243865, were genotyped by polymerase chain reaction -restriction fragment length polymorphism. Gene-environment interactions on risk of NAFLD was preliminarily investigated by generalized multifactor dimensionality reduction (GMDR) and further confirmed by unconditional logistic regression methods. After adjusting for covariates, increased risk of NAFLD were observed in subjects carrying TT/CT genotypes in rs3918242 ((Adjust)OR=1.64, 95% CI: 1.24, 2.11, P=0.006). However, decreased risk of non-alcoholic fat liver disease was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with CC carrier ((Adjust)OR=0.65, 95% CI: 0.47, 0.72, P=0.000).Interactions of central obesity with rs3918242 was preliminarily found by GMDR, with a maximum prediction accuracy (67.61%) and a maximum Cross-validation Consistency (10/10).The unconditional logistic regression method indicated central obesity-positive subject with genotype TT/CT had 4.54 times risk of NAFLD compared to central obesity-negative subjects with genotype CC (OR(add)(a)=4.54, 95% CI: 2.81, 7.21, P(add)(a)=0.000), which further confirmed the interactions. The results indicate that both rs3918242 and rs243865 is associated with risk of NAFLD. Furthermore, rs3918242 and central obesity have synergistic effects on risk of NAFLD. |
| DOI: |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |