People who carry a common mutation in a gene called SCARB1 – that regulates cholesterol – may have a higher risk of
developing heart disease, say the researchers behind a new study published in the journal PLOS ONE.
The study found a found a statistically significant link between a variant of a gene that controls for cholesterol and increased risk of heart disease.
The team – including members from the Universities of Virginia and Connecticut – looked at the link between a
mutation called the missense rs4238001 variant of SCARB1 – and the incidence of coronary heart disease in a group of 5,000
Americans taking part in the Multi-Ethnic Study of Atherosclerosis (MESA) sponsored by the National Heart Lung and Blood Institute.
The variant alters the type of protein that SCARB1 codes for, and thus interferes with cholesterol regulation. Previous
studies in mice and humans have shown this is linked to atherosclerosis – a potentially serious condition where arteries become
clogged up by fatty substances.
The team mapped the genetic makeup of the white, African-American and Hispanic-American participants and tracked episodes of
coronary heart disease over 7 years.
They found a statistically significant link between the SCARB1 variant and increased risk of heart disease across all
groups, but particularly among men and African-Americans.
Study leader Annabelle Rodriguez-Oquendo, an endocrinologist and professor at the University of Connecticut Health Center in
Farmington, and colleagues found the risk of developing heart disease was up to 49% higher among carriers of the rs4238001
variant than in the general population.
Their analysis showed African-American men carrying the rs4238001 variant fared the worst – they had the 49% higher risk of
developing heart disease, while white males had a 24% higher risk. Overall, men with the variant had a 29% higher risk.
Prof. Rodriguez-Oquendo says the rs4238001 variant is quite common. There is a test that clinicians can use to find out if
their patients are carriers so they can offer advice about preventing heart risk.
Having made the discovery about the link with heart disease, the team now wants to find out more about the underlying biology,
and how to fix it, as Prof. Rodriguez-Oquendo explains:
“We want to go deep in the cell, and figure out how to repair it. We’re really interested in understanding more
about how this protein gets chewed up and degraded faster.”
The team believes the answers will have implications for how we prevent heart disease and treat patients who carry the variant
gene. Approaches that involve adjusting hormone levels to alter cholesterol metabolism, may turn out to be more appropriate.
In a previous post at Johns Hopkins Medicine, Prof. Rodriguez-Oquendo showed how another variant of SCARB1 is linked to infertility in women. In that study – published in the journal Human
Reproduction – she and her team showed how the mutation appears to affect progesterone production, making it a likely
culprit in a substantial number of cases of female infertility.