Scientists have discovered common genetic variants influencing susceptibility to nonalcoholic fatty liver disease, according to a study published online in Nature Genetics. The risk variants vary in frequency among Hispanics, African Americans and European Americans and contribute to differences in disease prevalence among these ethnic groups.
Helen Hobbs, Jonathan Cohen and colleagues performed a genome-wide association study on a population of mixed ethnicity from the United States, focusing on common variation in protein-coding sequences. The group discovered a variant in a gene called PNPLA3 associated with increased hepatic fat levels and liver inflammation. The risk variant is most common in Hispanics, the group in the study sample most susceptible to the disease. The authors also found a second variant in PNPLA3 associated with lower hepatic fat content in African Americans, the group at lowest risk of the disease. The accumulation of excess fat in the liver, a condition known as hepatic steatosis, is associated with insulin resistance and other adverse consequences. In some individuals, hepatic steatosis promotes an inflammatory response in the liver known as steatohepatitis, which can progress to cirrhosis and liver cancer. Nonalcoholic fatty liver disease is the most common form of liver disease in Western countries. In the United States, Hispanics have a higher frequency of the disease than African Americans, with European Americans showing an intermediate prevalence. Author contacts: Helen Hobbs (University of Texas Southwestern Medical Center, Dallas, TX, USA) E-mail: helen.hobbs@utsouthwestern.edu Jonathan Cohen (University of Texas Southwestern Medical Center, Dallas, TX, USA) E-mail: jonathan.cohen@utsouthwestern.edu Abstract available online. (C) Nature Genetics press release.
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