Causes & Risk Factors

Genetic Cause

Sickle cell disease is caused by a mutation in the HBB gene on chromosome 11. This gene provides instructions for making a protein called beta-globin, which is a component of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen throughout the body.

The mutation causes the body to produce an abnormal type of hemoglobin called hemoglobin S (HbS). When oxygen levels are low, HbS can form stiff rods within the red blood cells, changing their shape from round to a crescent or "sickle" shape.

Inheritance Pattern

Sickle cell disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. These individuals are known as carriers or are said to have sickle cell trait.

Evolutionary Perspective

The sickle cell gene mutation is more common in people from parts of the world where malaria is or was common. It's believed that the sickle cell trait provided a survival advantage against malaria. People who have sickle cell trait (one copy of the HbS gene) are more resistant to malaria because the parasite that causes malaria has difficulty growing in the red blood cells of these individuals.

Risk Factors

The primary risk factor for sickle cell disease is having parents who both carry the sickle cell gene. The disease is more common among people whose ancestors came from:

• Africa
• Mediterranean countries (such as Greece, Turkey, and Italy)
• The Arabian Peninsula
• India
• Parts of Central and South America