Screening for Alpha Thalassemia in Healthy Volunteers
Screening for Alpha Thalassemia in Healthy Volunteers
Background:

 Alpha thalassemia is a blood disorder. It is caused by genetic deletions. Part of the DNA is
 missing from a group of genes called alpha globin. Alpha thalassemias are some of the most
 common genetic deletions. We are testing for alpha thalassemia trait. Alpha thalassemia trait
 is when someone has only two out of the normal four alpha globin genes. In some people, they
 lead to no symptoms. Others have changes that lead to disease, including mild anemia.
 Researchers want to learn more about alpha thalassemia and blood vessels. This may allow them
 to develop new treatments for blood diseases such as sickle cell disease.

 Objective:

 To better understand how alpha globin deletions in healthy people affect blood vessels.

 Eligibility:

 Healthy volunteers ages 18-39 who self-report African ancestry.

 Design:

 Participants will provide a one-time saliva sample. This can be by mail, in-person at a study
 event, or at NIH.

 Participants will get a small kit to collect their saliva sample. The kit has easy
 instructions. The sample does not need to be put in the refrigerator.

 Participants will spit a small amount of saliva (less than half a teaspoon) into a collection
 tube.

 Participants will close the funnel lid tightly, and then unscrew the funnel lid from the
 tube. They will then close the tube tightly with the small cap provided and shake the tube
 for 5 seconds.

 Participants will place the tube in the provided envelope and mail it to NIH. The specimen
 will be stored and processed in the lab.

 Participants may be invited to participate in more research studies, whether or not
 researchers find that they have alpha thalassemia trait.
Many of the complications of sickle cell disease, such as stroke, kidney damage, skin
 ulceration,pulmonary hypertension, and cardiac hypertrophy are prevented, delayed or reduced
 by inheritance of one of more deletions of the alpha globin genes. Our long-term research
 goal is to understand how deletions of alpha globin protect against the vascular
 complications of sickle cell disease.

 Deletions of alpha globin are common and found in approximately 5% of the world s
 population.They are especially common among Africans and people of African ancestry, as well
 as in India, China, and the Pacific Islands, where prevalence can range from 5 - 80%. A
 single deletion has little effect on the red blood cell, but two deletions can give rise to
 alpha thalassemia, a mild microcytic anemia. Patients with sickle cell disease who have two
 alpha globin deletions tend to have a higher hemoglobin level, smaller red blood cells, and a
 lower fraction of circulating reticulocytes consistent with decreased hemolysis and red cell
 turnover. They also have a lower number of dense or irreversibly sickled cells. These changes
 might explain why alpha globin deletions reduce the severity of sickle cell disease.

 However, a novel function for alpha globin as a regulator of endothelial nitric oxide (NO)
 has recently been identified that raises new questions about how alpha globin deletions
 protect against sickle cell disease. We hypothesize that individuals with two alpha globin
 deletions will have decreased gene expression and protein levels of alpha globin in vascular
 endothelium, permitting more NO to diffuse across the myoendothelial junction, compared to
 individuals who have all four alpha globin genes intact. In this protocol we will screen
 healthy volunteers to identify those with two alpha globin deletions; these individuals as
 well as matched controls will be referred to a separate protocol to undergo studies of
 vascular endothelial function.
-  INCLUSION CRITERIA:

 Subject report of the following:

 1. Age 18 - 39

 2. Self-report of African ancestry

 3. Willingness and legal ability to give and sign informed study consent

 EXCLUSION CRITERIA:

 There are no exclusion criteria for this screening protocol