Role of Tumor Necrosis Factor-a Promoter Polymorphism and Insulin Resistance in the Development of Non-alcoholic Fatty Liver Disease in Obese Children
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Purpose: Tumor necrosis factor-α (TNF-α) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-α promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M：F=74：37; mean age, 11.1±2.0 yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-α levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-α -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-α polymorphism at the -308 or the -238 loci between group I and group II + III (p=0.134 and p=0.133). The medians of HOMA-IR were significantly different between group I and group II + III (p=0.001), with significant difference between group II and group III (p=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus (p=0.061) or the -238 locus (p=0.207) in obese children. Conclusion: TNF-α promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.
Abstract
Purpose: Tumor necrosis factor-α (TNF-α) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-α promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M：F=74：37; mean age, 11.1±2.0 yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-α levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-α -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-α polymorphism at the -308 or the -238 loci between group I and group II + III (p=0.134 and p=0.133). The medians of HOMA-IR were significantly different between group I and group II + III (p=0.001), with significant difference between group II and group III (p=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus (p=0.061) or the -238 locus (p=0.207) in obese children. Conclusion: TNF-α promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.
참고문헌 (30)
- Ludwig J, "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease", Mayo Clin Proc, 55, pp.434~438 (1980)
- Powell EE, "The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years", Hepatology, 11, pp.74~80 (1990)
- Molleston JP, "Obese children with steatohepatitis can develop cirrhosis in childhood", Am J Gastroenterol, 97, pp.2460~2462 (2002)
- Lavine JE, "Nonalcoholic fatty liver disease in the pediatric population", Clin Liver Dis, 8, pp.549~558 (2004)
- Day CP, "Steatohepatitis: a tale of two “hits”?", Gastroenterology, 114, pp.842~845 (1998)
- Matteoni CA, "Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity", Gastroenterology, 116, pp.1413~1419 (1999)
- Polyzos SA, "Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines", Curr Mol Med, 9, pp.299~314 (2009)
- Bugianesi E, "Non-alcoholic fatty liver and insulin resistance: a cause-effect relationship?", Dig Liver Dis, 36, pp.165~173 (2004)
- Hotamisligil GS, "Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance", J Clin Invest, 95, pp.2409~2415 (1995)
- Uysal KT, "Protection from obesity-induced insulin resistance in mice lacking TNF-α function", Nature, 389, pp.610~614 (1997)
- Crespo J, "Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients", Hepatology, 34, pp.1158~1163 (2001)
- Hui JM, "Beyond insulin resistance in NASH: TNF-alpha or adiponectin?", Hepatology, 40, pp.46~54 (2004)
- Chu CJ, "Risk factors associated with non-alcoholic fatty liver disease in Chinese patients and the role of tumor necrosis factor-alpha", Hepatogastroenterology, 54, pp.2099~2102 (2007)
- Aller R, "Influence of insulin resistance and adipokines in the grade of steatosis of nonalcoholic fatty liver disease", Dig Dis Sci, 53, pp.1088~1092 (2008)
- Hajeer AH, "Influence of TNFα gene polymorphisms on TNFα production and disease", Hum Immunol, 62, pp.1191~1199 (2001)
- Valenti L, "Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease", Gastroenterology, 122, pp.274~280 (2002)
- Grove J, "Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis", Hepatology, 26, pp.143~146 (1997)
- Tokushige K, "Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis", J Hepatol, 46, pp.1104~1110 (2007)
- Wong VW, "Genetic polymorphisms of adiponectin and tumor necrosis factor-alpha and nonalcoholic fatty liver disease in Chinese people", J Gastroenterol Hepatol, 23, pp.914~921 (2008)
- Hu ZW, "Tumor necrosis factor-alpha gene promoter polymorphisms in Chinese patients with nonalcoholic fatty liver diseases", Acta Gastroenterol Belg, 72, pp.215~221 (2009)
- Aller R, "G308A polymorphism of TNF-alpha gene is associated with insulin resistance and histological changes in non alcoholic fatty liver disease patients", Ann Hepatol, 9, pp.439~444 (2010)
- Kleiner DE, "Design and validation of a histological scoring system for nonalcoholic fatty liver disease", Hepatology, 41, pp.1313~1321 (2005)
- 문진수, "2007 한국 소아 청소년 성장도표 : 개발 과정과 전망", Korean Journal of Pediatrics, 51(1), pp.1~25 (2008), 대한소아과학회
- Matthews DR, "Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man", Diabetologia, 28, pp.412~419 (1985)
- Strauss S, "Interobserver and intraobserver variability in the sonographic assessment of fatty liver", Am J Roentgenol, 189, pp.320~323 (2007)
- Brunt EM, "Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions", Am J Gastroenterol, 94, pp.2467~2474 (1999)
- Kim TH, "Tumor necrosis factor-α and interleukin-10 gene polymorphisms in Korean patients with inflammatory bowel disease", Korean J Gastroenterol, 42, pp.377~386 (2003)
- Tilg H, "Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of insulin resistance", Gastroenterology, 131, pp.934~945 (2006)
- Manco M, "Correlation of serum TNF-α levels and injury scores in pediatric nonalcoholic fatty", Am J Clin Pathol, 127, pp.954~960 (2007)
- Marchesini G, "Association of nonalcoholic fatty liver disease with insulin resistance", Am J Med, 107, pp.450~455 (1999)