Gene Variant Found Associated with Fetal Hemoglobin Levels Linked to Moderated Symptoms of Beta-thalassemia
Beta-thalassemia is a serious, potentially life-threatening disease
that affects red blood cells, cells that carry oxygen via hemoglobin
throughout the body. As part of the SardiNIA Study of Aging, supported
by the National Institute on Aging (NIA), a component of the National
Institutes of Health (NIH), scientists have found a genetic variant
in the BCL11A gene that can explain why some people with beta-thalassemia
seem to be protected from most dangerous symptoms. The findings
appear this week in Proceedings of the National Academy of
Sciences.
While all those affected in the Sardinia study population have
the same mutation in adult hemoglobin, the carrier of oxygen in
the red cells, some people experience less extreme symptoms than
others — mild enough that these individuals do not need to
undergo regular blood transfusions, usually a necessary treatment
for beta-thalassemia. People with this blood disorder do not have
enough hemoglobin binding to oxygen within their red blood cells
and are therefore weakened. They are also at risk for "hemolytic
crisis," a condition in which their red blood cells are destroyed
faster than their bodies can make new ones. It has been known that
some individuals escape hemolytic crisis because they retain a
high level of fetal hemoglobin (HbF), which is turned off at birth
in most people. The persistence of fetal hemoglobin seems to substitute
for the lack of adult hemoglobin sufficiently to moderate the course
of the disease.
Now it has been shown that variation in the BCL11A gene, discovered
through a genome-wide scan of 4,305 research participants in Sardinia
and representing a founder population with a high frequency of
beta-thalassemia, is strongly associated with elevated levels of
HbF and is specifically more common in the individuals with less
severe disease. Also in this study, researchers found
the same BCL11A variant associated with persistent HbF levels among
1,242 patients from the Cooperative Study of Sickle Cell Disease,
another disorder in which adult hemoglobin levels are depleted.
The study raises the possibility that manipulation of BCL11A levels
might be studied as a potential therapeutic intervention to alleviate
hemoglobin deficiencies that occur in people with beta-thalassemia
and sickle cell anemia.
In January 2008, Nature Genetics published
two papers on research from the SardiNIA Study on Aging completed
in collaboration with the Finland-United States Investigation of
Non-Insulin-Dependent Diabetes Mellitus Genetics study and the
Diabetes Genetics Initiative. These papers reported genome-wide
association study findings involving gene variants associated with
lipid levels and variants associated with height. Press releases
about these findings are available on the NIH website at http://www.nih.gov/news/health/jan2008/nia-13.htm (lipid
levels) and http://www.nih.gov/news/health/jan2008/nhgri-13.htm (height).
The NIA leads the federal government effort conducting and supporting
research on the biomedical and social and behavioral aspects of
aging and the problems of older people. For more information on
aging-related research and the NIA, please visit the NIA website
at www.nia.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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