PR85046

REYKJAVIK, Iceland, August 6, 2020, /PRNewswire=KYODO JBN/--

Genetic variability in cholesterol and phytosterol absorption affects

cardiovascular disease risk

Scientists at deCODE genetics, a subsidiary of Amgen, and their collaborators

from the Icelandic healthcare system, University of Iceland, the Copenhagen

University Biobank and the Danish Blood Donor Study, recently published a study

in European Heart Journal, with new findings that point to harmful effects of

dietary cholesterol and phytosterols.

It is well established that the "bad" cholesterol (also called non-HDL

cholesterol and LDL cholesterol) directly affects the development of

cardiovascular disease. Individuals who have high blood levels of bad

cholesterol, or are at high risk of heart disease for other reasons, are

generally advised to lower their cholesterol levels through lifestyle changes,

and sometimes receive treatment with cholesterol-lowering drugs such as statins.

Blood levels of cholesterol are affected by both genetics and the environment,

diet in particular, with the consumption of saturated fats, found primarily in

red meat and high-fat dairy foods, increasing blood cholesterol. However, the

importance of dietary cholesterol in the regulation of cholesterol levels in

the blood and the risk of heart disease has been the subject of controversy for

decades. Most foods that are rich in cholesterol are also high in saturated

fats with some exceptions, including eggs and shellfish.

Phytosterols are cholesterol-like molecules found in small amount in all plant

foods, including fruits, vegetables, nuts and legumes. Food enriched with high

amounts of phytosterols, mainly margarine and dairy products, is commonly

recommended as part of heart-healthy diet as it may decrease the absorption of

dietary cholesterol.

The transporter proteins NPC1L1 and ABCG5/8 control the absorption of dietary

cholesterol and phytosterols. NPC1L1 transports sterols from the intestinal

lumen into enterocytes where ABCG5/8 excretes less than half of the cholesterol

but most of the phytosterols back into the intestinal lumen. Thus, we generally

absorb about 50-60% of the intestinal dietary cholesterol but only 5% of

dietary phytosterols.

The authors studied the effects of sequence variants that modulate the function

of the ABCG5/8 transporter on blood levels of cholesterol and phytosterols and

the risk of coronary artery disease in large sample sets from Iceland, Denmark

and the UK Biobank. The effects of the sequence variants were measured in up to

147 thousand patients with coronary artery disease and 922 thousand individuals

without disease.

The study showed that individuals who harbor sequence variants that decrease

the function of ABCG5/8 transporter have increased blood levels of both

cholesterol and phytosterols and increased risk of heart disease. These results

confirm that dietary cholesterol affects blood levels of cholesterol and risk

of heart attacks. The results also demonstrate that people absorb variable

amounts of the cholesterol they consume.

The study also showed that the effect of the ABCG5/8 variants, influencing both

levels of cholesterol and phytosterol, on risk of heart disease, was greater

than of other cholesterol variants that do not affect phytosterol levels. These

results support the notion that phytosterols may contribute directly to

atherogenesis, raising questions about the safety of supplementing food with

phytosterols.

In the accompanying Editorial, Oliver Weingärtner states that "The study by

Helgadottir et al. is not only the best study so far to support the hypothesis

that variations at the ABCG5/ABCG8 locus is mechanistically involved in

atherosclerotic heart disease, but it also lends a strong impetus to study the

role of xenosterols in this process too."

Based in Reykjavik, Iceland, deCODE is a global leader in analyzing and

understanding the human genome. Using its unique expertise in human genetics

combined with growing expertise in transcriptomics and population proteomics

and vast amount of phenotypic data, deCODE has discovered risk factors for

dozens of common diseases and provided key insights into their pathogenesis.

The purpose of understanding the genetics of disease is to use that information

to create new means of diagnosing, treating and preventing disease. deCODE is a

wholly-owned subsidiary of Amgen (NASDAQ: AMGN).

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Contact:

Thora Kristin Asgeirsdottir

PR and Communications

deCODE genetics

+354 570 1909

+354 894 1909

SOURCE: DeCODE Genetics Inc