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APOC3 Variants Linked to Non-alcoholic Fatty Liver Disease

The two single-nucleotide polymorphisms in APOC3 gene also linked to insulin resistance

THURSDAY, March 25 (HealthDay News) -- Two single-nucleotide polymorphisms (SNPs) in the apolipoprotein C3 (APOC3) gene are associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD), according to research published in the March 25 issue of the New England Journal of Medicine.

Kitt Falk Petersen, M.D., of the Yale University School of Medicine in New Haven, Conn., and colleagues analyzed data from 95 healthy Asian Indian men. Subjects underwent genotyping of two SNPs in the APOC3 gene previously linked to hypertriglyceridemia (rs2854116 and rs2854117). Additional testing included proton magnetic resonance spectroscopy to measure hepatic triglyceride content.

The researchers found that 38 percent of variant-allele carriers had NAFLD, compared to none of the wild-type homozygotes. Those with NAFLD had insulin resistance. The association between variant alleles and NAFLD was confirmed in another group of non-Asian Indian men. Subjects carrying the APOC3 variant alleles had a 30 percent increase in fasting plasma apolipoprotein C3 concentration and a 60 percent increase in fasting plasma triglycerides. Plasma triglyceride and retinyl fatty acid ester concentrations were higher after a fat-tolerance test, while plasma triglyceride clearance was lower.

"Eventually, doctors may be able to identify patients who are at risk for hepatic steatosis, as well as patients with steatosis who are particularly at risk for non-alcoholic steatohepatitis. Preventive strategies and treatments can then be introduced to minimize the health risks attributable to fatty liver," the author of an accompanying editorial writes.

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