Study Reveals Why Some People Develop Medical Complications of Obesity

New gene sites that affect nonalcoholic fatty liver disease (NAFLD)have been identified by scientists.

NAFLD is a condition where fat accumulates in the liver (steatosis) and can lead to liver inflammation (nonalcoholic steatohepatitis or NASH) and permanent liver damage (fibrosis/cirrhosis).

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NAFLD affects anywhere from 11percent to 45 percent of some populations and is associated with obesity, hypertension, and problems regulating serum lipids or glucose.

"These findings will help us to better diagnose, manage, and treat NAFLD in the future and help explain why some but not all people with obesity develop particular complications of obesity; some carry genetic variants that predispose them to some but not other metabolic diseases," said lead author Elizabeth K. Speliotes, Assistant Professor at the University of Michigan.

Speliotes' team, called the GOLD (Genetics of Obesity-related Liver Disease) Consortium, meta-analyzed genome wide association data for liver steatosis from 7,126 individuals and then followed up top associating variants in cases of NASH/fibrosis from the NASH-Clinical Research Network that were genetically matched to controls from the MIGen study to find the five variants that reproducibly associate with NAFLD.

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All the genetic variants found increased fat deposition in the liver. However, only some affected development of inflammation/permanent damage of the liver or development of serum lipid/glucose abnormalities.

"We found that approximately one quarter of the variation in NAFLD is influenced by genetic factors, and the loci we identified in the study account for about 20 percent of that genetic component," Ingrid Borecki, senior author on the paper said.

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Interestingly, the pattern of effects on multiple metabolic traits at two associated loci were identical and the genes closest to the best association signal at these loci are predicted to play a role in subsequent steps in triglyceride breakdown.

Triglycerides are the major form of fat stored in the liver in NAFLD. This suggests that defects in triglyceride breakdown may contribute to development of NAFLD.

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Source-ANI