Obesity significantly amplifies the effects of three gene variants that increase risk of nonalcoholic fatty liver disease (NAFLD), according to a new international study.
NAFLD, which in its most serious form can lead to chronic liver disease (cirrhosis) and liver cancer, is a growing problem associated with the obesity epidemic.
Despite intense study, the relationship between obesity and NAFLD had remained unresolved.
Of the three gene variants, or alleles, examined in this study, the strongest genetic-environmental interactions were found in the PNPLA3 gene variant, the first genetic cause of NAFLD ever identified.
The findings are published in the Nature Genetics.
“While all obese individuals who have fatty liver disease would benefit from weight loss, our data suggest that those who have the risk allele in PNPLA3 are likely to benefit mores,” said one author.
The National Institutes of Health (NIH) describes NAFLD as one of the most common causes of liver disease in the United States.
It estimates that 30 to 40 percent of U.S. adults have simple fatty liver, a buildup of fat in the liver without significant inflammation or cell damage.
An estimated 3 to 12 percent of adults in the U.S. have a more serious form of NAFLD, called nonalcoholic steatohepatitis (NASH), a buildup of liver fat with inflammation and cell damage that can lead to cirrhosis and is associated with liver cancer.
“If you are thin, then you are unlikely to have excess fat in your liver even if you have the PNPLA3 risk alleles,” said another author. “On the other hand, if you are obese and lack the variant, then there is a good chance that you won’t have excess fat in your liver.
“But if you are obese and do have the variant – particularly if you have two copies of the variant – you are very likely to have excess fat in your liver,” he said, adding that these findings may help resolve some puzzling aspects of the relationship between obesity and fatty liver disease.