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Gene Found in Amish Helps Protect Their Hearts

HealthDay News
by By Amy Norton HealthDay Reporter
Updated: Dec 3rd 2021

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FRIDAY, Dec. 3, 2021 (HealthDay News) -- A rare gene variant discovered among Amish people may help lower "bad" cholesterol and protect against heart disease, a new study suggests.

Researchers found that among nearly 7,000 Amish people, the gene variant was tied to reductions in both LDL cholesterol and fibrinogen -- a protein that is a marker of inflammation and linked to heart disease risk.

There was also evidence of protection against heart disease itself: Among more than 500,000 people in the general population, carriers of certain variants in the gene had a 35% lower risk of coronary artery disease.

But while the gene variant is rare, experts said its benefits could potentially be captured in a pill.

"We may be able to make a drug that mimics its effects," explained lead researcher May Montasser, an assistant professor at the University of Maryland School of Medicine.

Heart disease experts who reviewed the study agreed -- though, they said, much work remains.

"This has the potential to be a therapeutic target," said Dr. Sadeer Al-Kindi, co-director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease at University Hospitals Harrington Heart and Vascular Institute in Cleveland.

Al-Kindi praised the design of the study, saying, "It tells a compelling story."

Montasser's team started by analyzing the genes of about 6,900 members of the Old Order Amish (OOA) community of Lancaster County, Pa. Nearly all of the OOA community can trace their ancestry back to a small number of "founder families." Because of that, and their similar lifestyle, they are considered an ideal population for studies trying to isolate genes that, in the general population, are rare.

Here, the researchers discovered that a particular variant in a gene called B4GALT1 -- carried by 6% of the Amish group -- was associated with lowered levels of both LDL cholesterol and fibrinogen.

While 6% is not a huge figure, it is significant in comparison to the general population: Montasser's team was able to find the gene variant in only eight of 140,000 genomes from non-Amish people that are included in a government research database.

Next, Montasser and her colleagues turned to databases with genetic information on more than 500,000 British and U.S. participants. Since the gene variant discovered in the Amish group is so rare, they looked at whether a collection of similar variants in B4GALT1 was linked to heart disease risk in those two databases.

It turned out it was: People with the variants were about 35% less likely to be diagnosed with coronary artery disease than other people were.

Finally, the researchers backed up the findings in lab mice -- showing that LDL and fibrinogen dropped in mice that were genetically engineered to carry the B4GALT1 variant.

Before it all can be translated into a therapy, there is plenty of work to do.

The researchers need to learn more about the gene variant's mechanisms of action, Montasser said, and whether it has any negative health effects.

So far, she noted, there is no evidence of harm.

There are, of course, already medications for lowering LDL, including statins and injection drugs called PCSK9 inhibitors.

In theory, a medication that would lower both LDL and fibrinogen could be better than drugs that lower LDL only. But, Al-Kindi said, it's not known whether high fibrinogen, per se, contributes to heart disease -- or that lowering it would provide extra protection.

Dr. Douglas Mann, editor-in-chief of Journal of the American College of Cardiology: Basic to Translational Science, made a similar point.

It's possible that any medication developed from this research could hit "multiple targets," Mann said.

But, he added, "that remains to be proven."

And given the existence of effective, safe and cheap LDL-lowering drugs, Mann noted, a new therapy would need to be well-tolerated and "not break the bank."

The findings were published Dec. 2 in the journal Science.

More information

The American Heart Association has advice on lowering heart disease risk.

SOURCES: May Montasser, PhD, assistant professor, medicine, University of Maryland School of Medicine, Baltimore; Sadeer Al-Kindi, MD, co-director, Center for Integrated and Novel Approaches in Vascular-Metabolic Disease, University Hospitals Harrington Heart and Vascular Institute, and assistant professor, medicine and radiology, Case Western Reserve University School of Medicine, Cleveland; Douglas Mann, MD, editor-in-chief, JACC: Basic to Translational Science; Science, Dec. 2, 2021