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Pediatrics

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.

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Acknowledgements

We are indebted to Jyh-Feng Lu for laboratory work, and to Chien-Hao Chen for assistance with the statistical analysis. This work was supported by research grants from the Far Eastern Memorial Hospital (FEMH- 2011- C - 30 and FEMH- 2012- C- 040).

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Correspondence to Y-H Ni.

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Chang, PF., Lin, YC., Liu, K. et al. Heme oxygenase-1 gene promoter polymorphism and the risk of pediatric nonalcoholic fatty liver disease. Int J Obes 39, 1236–1240 (2015). https://doi.org/10.1038/ijo.2015.46

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