The discovery of a genetic
variant that is relatively common among people of Polynesian ancestry, but
incredibly rare in most other populations, is giving clues to the genetic
underpinnings of high cholesterol in all people, according
to new research led by University of Pittsburgh School of Public Health geneticists
in partnership with several other groups, including the University of Otago and
the Samoan health research community.

The surprising finding,
published this week in the journal Human Genetics and Genomics Advances,
demonstrates the importance of ensuring diversity in genetic databases.

High cholesterol is a major
cause of disease burden in countries of all income levels, is a risk factor for
heart disease and stroke, and is estimated to cause 2.6 million deaths annually
worldwide, according to the World Health Organization.

Carlson and her team built their study to
explore a signal that popped up in a large genome-wide survey looking for genes
associated with lipids, or fats, in the body. It suggested that a gene variant
on chromosome 5 could be associated with cholesterol. The team set out to “fine map” the region using genetic data
from 2,851 Samoan adults from the Obesity, Lifestyle, And Genetic Adaptations
(OLAGA, which means “life” in Samoan) Study Group who had also provided
health information, including lipid panels. To double-check the finding, the
team looked for the association in 3,276
other Polynesian people from Samoa, American Samoa and Aotearoa New Zealand,
and the same connection between the variant and cholesterol was seen in them.

Using data from the western Polynesian Samoan
participants, the team was able to fill in the missing information around the
region they were interested in on chromosome 5. This led them to BTNL9 – a gene that directs the production
of the BTNL9 protein. Proteins
typically signal to cells to perform actions, though scientists still haven’t
characterized the precise role of the BTNL9 protein.

4It turned out that
Polynesian people with low levels of HDL “good” cholesterol and high levels of
triglycerides had a “stop-gain” variant in BTNL9, which means the gene was
being directed to stop doing its protein-production job, a
strong hint that the BTNL9 protein is involved in helping cells maintain
healthy cholesterol levels.

Reference:

JENNA CARLSON et al,Human Genetics and Genomics
Advances,DOI:10.1016/j.xhgg.2022.100155

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