Genetic variants linked to fatty liver disease in children with obesity

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of pediatric chronic liver disease. New research has found that the genetic variant patatin-like phospholipase domain containing protein-3 (PNPLA3) acting in conjunction with the glucokinase regulatory protein (GCKR) is associated with increased susceptibility to fatty liver disease in children with obesity.

The study determined that the PNPLA3 and GCKR single nucleotide polymorphisms (SNPs) were responsible for up to 39% of the hepatic fat content (HFF%) in this pediatric population.

Researchers recruited 455 children and adolescents with obesity who underwent genotyping and fasting triglycerides and lipoprotein particles testing. Participants (mean age, 13 years) included 181 white, 139 black, and 135 Hispanic children. The researchers measured HFF% using magnetic resonance imaging in a subset of 142 children.

Results showed that the minor allele rs1260326 in the GCKR gene is associated with higher triglycerides levels and higher levels of very-low-density lipoproteins in white and black children. The GCKR SNP was associated with fatty liver in each of the 3 ethnic groups. A joint effect between PNPLA3 and GCKR SNPs was responsible for 32% of HFF% in white children, 39% in black, and 15% of Hispanic children.

The researchers suggest that the GCKR variant may lead to accumulation of fat in the liver through an increase in hepatic triglyceride production, although whether the variant confers increased risk factors for cardiovascular disease remains unclear.

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