Missense Variant in B4GALT1 Gene Linked to 33% Reduction in Heart Disease Risk, Reveals New Therapeutic Pathway

December 8, 2021/BioValleyBIOON/---In a new study, researchers from the University of Maryland School of Medicine and RegeneronGeneticsResearchers at the Regeneron Genetics Center have collaborated to discover a new genetic variant, which is associated with lower levels of low-density lipoprotein (LDL) cholesterol that damages the heart and a clotting protein called fibrinogen (FIB). This appears to significantly reduce a person's risk of developing heart disease. According to the study, although this genetic variant is extremely rare in the general population (less than one in ten thousand), about 12% of people in the Amish community in Lancaster County, Pennsylvania, have been found to carry this genetic variant.The relevant research findings were published in the December 2, 2021 issue of the journal Science, with the title "Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen”。

Scientists have long known about gene mutations related to cholesterol levels. However,This is the first time they have found that a gene variant can significantly reduce the levels of two risk factors for heart disease, thereby reducing an individual’s risk of heart disease. This discovery has the potential to lead to new treatments that may help prevent arterial blockages, blood clots, and cardiovascular diseases.

May Montasser, Ph.D., Assistant Professor of Medicine at the University of Maryland School of Medicine and corresponding author of the paper, said, "Using data from more than 500,000 ordinary people, we found that individuals carrying this variant have a 35% lower risk of developing heart disease compared to those who do not carry it. This genetic variant appears to regulate the synthesis of cholesterol and fibrinogen or accelerate their clearance from the bloodstream, thus protecting the heart. This discovery could lead to targeted drugs that mimic the effects of this variant, helping to keep arteries free from plaque and blood clots.”

The gene sequencing of samples from nearly 7,000 Amish study participants was conducted at the Regeneron Genetics Center.GeneticsThe study center has been conducting research since 1995, with participants involved in genetic studies at the University of Maryland School of Medicine.These authors found that a missense variant of the B4GALT1 gene was associated with a reduction in LDL cholesterol by nearly 14 mg/dL and FIB by nearly 30 mg/dL. After identifying the variant, they tested its effects in mice that had been genetically modified to express the variant.

Image from CC0 Public Domain.

Co-author of the paper, RegeneronGeneticsGiusy Della Gatta, Ph.D., Senior Scientist at the Regeneron Genetics Center, said, "Mice models encoding this gene variant also exhibited reductions in LDL cholesterol and FIB levels, confirming the effect of this variant. Such models represent a valuable tool for uncovering molecular mechanisms that may help protect against cardiovascular disease.”

The Amish community is an ideal place for genetic research because their common ancestry and homogeneous lifestyle make it easier for scientists to find new connections between genes and health. The co-author of the paper, Dr. Alan Shuldiner, Deputy Director of Personalized and Genomic Medicine at the University of Maryland School of Medicine, established the Amish Research Clinic in Lancaster County, Pennsylvania. The clinic's research has discovered new links in type 2...DiabetesAnd the genes that play a role in heart disease, as well as the genes that determine why some people do not respond to the anticoagulant drug Plavix.

"This is a groundbreaking discovery that would not have been possible without the participation and cooperation of the Amish community. We are extremely grateful for their continued commitment to the research and development of precision medicine," said E. Albert Reece, MD, PhD, MBA, Distinguished University Professor and Dean of the University of Maryland School of Medicine. (Bioon.com)

References:

May E. Montasser et al. Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. Science, 2021, doi:10.1126/science.abe0348.