Relevance of TNF-α gene polymorphisms in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is one of the most prevalent liver diseases worldwide. Its etiology is multifactorial and genetic factors most likely play a role. Genome-wide association studies have identified the first candidate genes, including patatin-like phospholipase 3, a lipase that is involved in triglyceride metabolism. Several other genetic variants have been identified, although with less convincing evidence. These genetic variants encode for molecules regulating insulin signalling, lipid metabolism, inflammation or fibrogenesis. Whereas the biological functions of TNF-α have been demonstrated to play an important role in the regulation of insulin resistance, liver inflammation and lipid accumulation, further genetic studies are needed to clarify whether and which TNF-α genetic variants predispose to the development of nonalcoholic steatohepatitis, the inflammatory component of nonalcoholic fatty liver disease.