Alcohol affects levels of cholesterol through epigenetics

In an analysis of the epigenomes of people and mice, researchers discovered that drinking alcohol may induce changes to a cholesterol regulating gene. The findings suggest that these changes to the gene, PCSK9, may be responsible for some of the differences in how cholesterol is processed in people who drink alcohol, or may affect those taking a relatively new class of PCSK9 cholesterol-lowering drugs designed to reduce LDL cholesterol.

Chronic alcohol use can have detrimental effects on the liver and the cardiovascular system. Regulation of PCSK9 seems to correlate with this pattern and may be a significant underlying factor behind the variations in the relationship between cholesterol and cardiovascular disease when it comes to alcohol use. Researchers measure how drinking of alcohol can leads to changes in which genes are expressed.

They examined information from DNA chips- microarrays that can show which genes have chemical methyl groups added across the whole genome. These chips looked at about 500,000 methyl groups at a time. methylation affects the level of gene expression. The researchers used different sets of data: DNA from the brains of deceased people with documented alcohol dependence compared to healthy controls and DNA from blood samples of people who had documented alcohol dependence with healthy controls.

When the investigators cross-compared epigenetic data from the sets of data to find out what changes occurred in common in the two data sets and what changes did not, the common factor highlighted the gene PCSK9. The human liver samples from people with alcohol dependence who underwent a liver transplant and noticed a similar pattern: more methylation on PCSK9 and unexpectedly lower PCSK9 protein levels. In samples from people who abused alcohol, the researchers detected that PCSK9 gene expression was only a third of the level in people who didn't abuse alcohol.

Alcohol is metabolized by the liver and can cause liver damage if used in large amounts over long periods of time. In people, PCSK9 is found at its highest levels in liver, but is also found in other tissues, such as brain and blood. PCSK9 binds to the bad cholesterol receptors and blocks uptake and breakdown of bad cholesterol by cells, leading to accumulation in the bloodstream, where it presumably clogs arteries.
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