Protein Linked To Elevated BMI In People Of Americ

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Protein Linked To Elevated BMI In People Of American Indian And
Mexican Ancestry Discovered By U Of M


*University of Minnesota researchers have discovered a variant of a
common blood protein, apolipoprotein C1, in people of American Indian
and Mexican ancestry that is linked to elevated body mass index (BMI),
obesity and Type 2 diabetes.

The finding were published in the /International Journal of Obesity./

Lead investigator Gary Nelsestuen, a professor in the College of
Biological Sciences' department of biochemistry, said the abnormal
protein may promote metabolic efficiency and storage of body fat when
food is abundant. This could have provided a survival advantage to
American Indians in the past when food was scarce. The discovery can be
used to identify those who are at risk for diabetes and to guide diet
and lifestyle choices to prevent diabetes.

Apolipoprotein C1 is a component of high density lipoprotein (HDL) and
low density lipoprotein (LDL). HDL cholesterol is often referred to as
good cholesterol, while LDL is called bad cholesterol. The common form
of C1 tends to be found in the high-density protein complexes (HDL) that
ferry cholesterol to storage depots in the body and are linked to lower
cardiovascular disease risk. But the variant form of C1 tends to become
part of low density protein complexes (LDL), which transport cholesterol
to arterial walls and are associated with higher cardiovascular disease
risk. Thus, having the variant could tip the balance of cholesterol
carriers and lead toward depletion of HDL-also a risk factor for heart
disease. The variant differs from the normal protein by a single change
in one of its 57 amino acids.

Among 1500 subjects from widely divergent genetic backgrounds, the
variant was found in 35 of 228 persons with American Indian ancestry and
in 10 of 84 persons with Mexican ancestry. The average body mass index
(BMI) of persons with the variant protein was 9 percent higher and the
diabetes rate 50 percent higher among study subjects and their parents.
Parents were included because type 2 diabetes often doesn't appear until
later in life.

This project has been a departure for Nelsestuen, who has made important
discoveries related to blood coagulation proteins involved in bleeding
disorders such as hemophilia and coagulation disorders such as sepsis
and thrombosis. The university has licensed these proteins to three
pharmaceutical companies who are developing them as therapeutic agents.
Nelsestuen is recognized on the university's Wall of Discovery for some
of these achievements.

Nelsestuen used income from the blood coagulation protein licenses and
his endowment from the Samuel Kirkwood Chair to support the research
that led to finding the abnormal variant of C1 lipoprotein.

The funds were used to apply new proteomics technology to screen blood
samples for proteins related to disease. This type of protein screening
is often described as "discovery" research. In its purest form,
proteomics discovery research looks for abnormal proteins in what seems
like a random process.

"This type of research is often dismissed as a fishing expedition by
funding agencies," Nelsestuen said. "But our finding shows the value of
discovery research and of having unrestricted funds to pursue it."

Nelsestuen's interest in education of minority graduate students
provided many of the connections to the communities that became involved
in this research. Former student Michael Martinez, helped establish a
collaboration with Kenneth McMillan, medical director of the American
Indian Community Development Corporation in Minneapolis, and Cristina
Flood-Urdangarin of St. Mary's Health Clinics in St. Paul.

Nelsestuen's next steps will be to expand the study to the Turtle
Mountain Indian Reservation in North Dakota and the Cheyenne River
Indian Reservation in South Dakota.

"I hope that this discovery will ultimately lead to a Minnesota center
for research on minority health issues that can deliver actual health
benefits to these communities," Nelsestuen said.