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Gene variant found associated with fetal hemoglobin levels linked to moderated symptoms of beta-thalassemia



January 30, 2008

Megan Homer | 301-496-1752 | nianews3@mail.nih.gov



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 www.nih.gov/news/health/jan2008/nia-13.htm (lipid levels) and 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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