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28-06-2011 | Cardiometabolic | Article

No link between APOC3 gene gene variants and liver steatosis

Abstract

Free abstract

MedWire News: Genetic variants of apolipoprotein C3 (APOC3) do not appear to have any influence on lipid profiles, or the prevalence of insulin resistance or fatty liver disease, a study of obese Italian adults shows.

This lack of association has now been consistently reported in European-American, African-American, and Hispanic-populations - calling into question a previously proposed biological mechanism, say Marco Baroni (University of Cagliari, Italy) and colleagues.

As many as 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) develop steatohepatitis, which is characterised by the presence of triglycerides stored as large lipid droplets in the cytoplasm of hepatocytes.

Elevated plasma APOC3 levels positively correlate with plasma triglyceride concentrations in hypertriglyceridemic individuals, apparently owing to the fact that APOC3 inhibits lipoprotein lipase and triglyceride clearance.

In a prior study, two sequence variants in the promoter of APOC3 (rs2854116 and rs2854117) were associated with hypertriglyceridaemia, nonalcoholic fatty liver disease, and insulin resistance in lean individuals of South Asian descent.

For the current study the researchers genotyped 585 unrelated obese Italians for these single nucleotide polymorphisms (SNPs) and performed oral glucose tolerance tests in addition to assessing alanine transaminase (ALT) and aspartate transaminase (AST) as markers of liver injury.

The study participants were divided into two groups: those homozygous for the wild-type alleles at both SNPs (-482C and -455T alleles) and those who were carriers of at least one variant allele (-482T or -455C) or both.

There were no significant differences between wild-type and variant allele carriers in terms of ALT, with levels of 27 and 29 U/l, respectively, nor AST at 19 and 20 U/l, respectively.

The researchers also found no significant difference in the proportion of individuals with pathologic serum levels of ALT (defined as >40 U/l), at 40.6% and 59.4% for wild-type homozygous and variant-allele carriers, respectively.

Likewise, lipid profile insulin concentrations, glucose tolerance, and insulin sensitivity were similar in the two groups.

"It could be argued that, in the context of the insulin resistance associated with obesity, the APOC3 variants are unable to induce further actions on lipid levels," Baroni et al comment in the journal Lipids in Health and Disease.

"However, we should point out that when we looked only at carriers of the variant alleles with normal insulin sensitivity, we did not observe any association with indices of fatty liver disease and lipid levels, suggesting that also in this state the APOC3 variants are not influencing [triglyceride] concentrations," they add.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Andrew Czyzewski