Heme oxygenase-1 gene promoter polymorphism and the risk of pediatric nonalcoholic fatty liver disease

• Published in: International Journal of Obesity 2015-08, Vol.39 (8), p.1236-1240
• Main Authors: Chang, P-F, Lin, Y-C, Liu, K, Yeh, S-J, Ni, Y-H
• Format: Article
• Language: English
• Subjects: 38/23; 45/77; 692/499; 692/699/1702/393; Adolescent; Age; Alanine; Alanine transaminase; Alleles; Anthropometry; Biomarkers; Body mass index; Child; Children; Confidence intervals; Development and progression; Epidemiology; Fatty liver; Female; Gene polymorphism; Genetic Predisposition to Disease - genetics; Glucose; Glucose metabolism; Health Promotion and Disease Prevention; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - genetics; Hepatitis; Homeostasis; Hospitals; Humans; Insulin; Insulin Resistance; Internal Medicine; Liver; Liver diseases; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolic Diseases; Metabolism; Microsatellite Repeats; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - genetics; Obesity; Obesity in children; original-article; Oxidation resistance; Oxidative stress; Oxidative Stress - genetics; Oxygenase; Pathogenesis; Patients; Pediatric Obesity - complications; Pediatric Obesity - epidemiology; Pediatric Obesity - genetics; Pediatrics; Polymorphism; Polymorphism, Genetic; Promoter Regions, Genetic; Public Health; Risk analysis; Risk Factors; Taiwan - epidemiology; Ultrasonic imaging; Ultrasound
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2015.46

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.