University of Maryland School of Medicine (UMSOM) and the Regeneron Genetics Center (RGC) researchers have uncovered a new gene variant linked to lower heart-damaging LDL cholesterol and fibrinogen levels. It also includes issues such as blood clotting protein that appears to reduce a person’s risk of heart disease.
An Amish Gene Variant Is Linked To A Lower Risk Of Heart Disease
According to a study published today in the journal Science, while the gene mutation is extremely rare in the general population, it is found in roughly 12% of those living in the Lancaster County, Pennsylvania Amish community.
Gene alterations linked to cholesterol levels have long been known to scientists. However, this is the first time they’ve discovered a gene mutation that can considerably lower the levels of two heart disease risk factors, lowering a person’s risk of heart disease as a result.
The discovery could pave the way for new medicines to avoid clogged arteries, blood clots, and cardiovascular disease. A DNA mutation discovered decades ago in an Amish community appears sufficient to extend people’s lives by ten years and reduce their risk of diabetes.
SERPINE1 is a gene that produces a protein called PAI-1, which stimulates the aging process. However, six generations ago in an Amish community, a defective variant of this gene emerged, causing people who carry one copy of the variant to generate half as much of the age-promoting protein. Researchers wondered if persons who carry the gene have a longer life expectancy.
We found that people who carried this variant had a 35 percent lower risk of heart disease compared to those who did not,” said study leader May Montasser, Ph.D., Assistant Professor of Medicine at UMSOM and a member of UMSOM’s Program for Personalized and Genomic Medicine.
“The genetic mutation appears to either control or expedite the removal of cholesterol and fibrinogen from the circulation, which protects the heart.” This discovery could lead to tailored medications that replicate the activity of this variation to prevent plaque and clots in arteries.”
The RGC performed genetic sequencing on samples from roughly 7,000 Amish study participants who have been involved in genetic research with UMSOM since 1995.
According to the study, a genetic mutation in the gene B4GALT1 was linked to a roughly 14 mg/dL lower LDL cholesterol and nearly 30 mg/dL lower fibrinogen. They evaluated the mutation’s effects in mice that had been genetically engineered to express the variant after it was discovered.
“The mouse model encoding for this gene mutation revealed decreased levels of LDL cholesterol and fibrinogen, demonstrating the effect of this variant,” said study leader and RGC senior staff scientist Giusy Della Gatta, Ph.D. “This model is a priceless tool for deciphering the molecular mechanisms that aid in the prevention of cardiovascular disease.”
The Amish community is suitable for genetic studies because of its common heritage and similar lifestyle, making it easier for scientists to discover new linkages between genes and health. Alan Shuldiner, MD, co-author of the study and Associate Dean for Personalized and Genomic Medicine at UMSOM, developed the Amish Research Clinic in Lancaster, Pennsylvania.
The clinic’s research has uncovered genes linked to type 2 diabetes and heart disease and a gene involved in determining why some patients don’t respond to the blood thinner Plavix.
E. Albert Reece, MD, Ph.D., MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K also went through the research by experts.
Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, said, “This is a ground-breaking finding that would not have been possible without the participation and partnership of the Amish community.” “We are grateful for their continued dedication to precision medicine research and advancement.”
