Chang P-F, Lin Y-C, Liu K, Yeh S-J, Ni Y-H
1] Department of Pediatrics, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan [2] Department of Healthcare Administration, Oriental Institute of Technology, Pan-Chiao, New Taipei, Taiwan.
Department of Pediatrics, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan.
Int J Obes (Lond). 2015 Aug;39(8):1236-40. doi: 10.1038/ijo.2015.46. Epub 2015 Apr 3.
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.
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.
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).
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.
氧化应激和胰岛素抵抗状态被认为是儿童非酒精性脂肪性肝病（NAFLD）发病机制的关键组成部分。血红素加氧酶（HO）在抵御氧化应激中起重要作用。本研究旨在评估肥胖儿童中HO-1基因启动子多态性及胰岛素抵抗与NAFLD的关联。
共招募101名6至17岁的肥胖儿童。测量人体测量学指标、血清生化变量以及葡萄糖和胰岛素代谢的生物标志物。我们筛查了这些肥胖儿童中HO-1基因启动子中（GT）n重复序列的等位基因频率。通过肝脏超声检查确定NAFLD。由于（GT）n重复序列数量的分布呈双峰分布，我们将等位基因分为两类：S类包括较短（27）的重复序列，L类包括较长（⩾27）的重复序列。我们评估了HO-1基因启动子中（GT）n重复序列长度对儿童NAFLD的影响。
101名肥胖受试者中，27名（26.7%）患有NAFLD。携带L等位基因（L/L和L/S）的患者丙氨酸氨基转移酶水平高于携带S等位基因（S/S）的患者（46.2±49.3 IU|(-1) 对30.2±20.1 IU|(-1)；P=0.027）。儿童NAFLD的显著危险因素为携带L等位基因（L/L和L/S）的患者（比值比（OR）=18.84；95%置信区间（CI）：1.45 - 245.22；P=0.025）、胰岛素抵抗的稳态模型评估（OR=1.40；95%CI：1.07 - 1.83；P=0.014）和年龄（OR=1.24；95%CI：1.03 - 1.50；P=0.025）。
在这项基于医院的研究中，HO-1基因启动子中GT重复序列较长且存在胰岛素抵抗的肥胖儿童易患NAFLD。
