Pediatr Gastroenterol Hepatol Nutr.  2012 Mar;15(1):44-51.

Role of Tumor Necrosis Factor-alpha Promoter Polymorphism and Insulin Resistance in the Development of Non-alcoholic Fatty Liver Disease in Obese Children

• Yang HR
• Ko JS
• Seo JK

Abstract

PURPOSE
Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-alpha -308 and -238 polymorphisms were evaluated.
RESULTS
There were no differences in TNF-alpha 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-alpha 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.

Keyword

TNF-alpha polymorphism; Insulin resistance; Fatty liver; Obesity; Child

MeSH Terms

Adult
Child
Fatty Liver
Genotype
Homeostasis
Humans
Insulin
Insulin Resistance
Obesity
Tumor Necrosis Factor-alpha
Fatty Liver
Insulin
Tumor Necrosis Factor-alpha

Figure

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  Fig. 1 The medians of HOMA-IR were significantly different among the 3 groups based on the status of NAFLD in obese children (p=0.001) (HOMA-IR: insulin resistance determined by homeostasis model assessment, NAFLD: non-alcoholic fatty liver disease, NASH: non-alcoholic steatohepatitis).

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