Sickle cell anaemia (SCA) affects hundreds of thousands of people in Africa. A study conducted in Cameroon by a University of Cape Town (UCT) professor may offer hope for people who suffer from the disease. The research took place in Cameroon.
Sickle cell anaemia is the most serious in a group of disorders known as sickle cell disease. It is an inherited red blood cell disorder in which there aren’t enough healthy red blood cells to carry oxygen throughout the body.
It is caused by a mutation in a single gene, responsible for the production of the protein haemoglobin. Making up 70% of the content of red blood cells, haemoglobin is essential for transporting oxygen throughout the body.
Prof Ambroise Wonkam, Principal Investigator and Director of Genetic Medicine of African Populations in the Division of Human Genetics at the University of Cape Town, said though the condition was identified more than 100 years ago, a definitive treatment is still not widely available.
Normally, the flexible, round red blood cells move easily through blood vessels. In sickle cell anaemia, the red blood cells are shaped like sickles or crescent moons. These rigid, sticky cells can become stuck in small blood vessels, which can slow or block blood flow and oxygen to other parts of the body.
“Among the 300,000 babies born with the condition every year, 80% are in Sub-Saharan Africa,”. It is, in essence, an African disease,” said Wonkam.
Despite the prevalence of SCA in Africa, medical care has been less than optimal.Wonkam said it has been shown that due to the lack of medical interventions in most African settings, at least 50% of African children with SCA will die before their fifth year.
However, the same regions of Sub-Saharan Africa are also home to SCA patients who are 50-60 years old.“Why is it that some people, who live in an environment that is not favourable in terms of health care access and stressors including high temperatures, malaria and other infections — manage to survive while others die at a much younger age? ” asked Wonkam “Our hypothesis is that these long survivors living with SCA may be protected by some genetic factors,” he notes.
To test this, Wonkam and his team recruited SCA patients 40 years and older who had received the minimal medical intervention, as well as a control group who had suffered strokes, which is one of the severe effects of SCA, and an intermediate group who were under 40 and never had a stroke
In the study, published in the journal Clinical and Translational Medicine, the team found genetic modifiers of long-term survival in individuals with SCA.People who had survived longer had recurrent changes in specific genes, and patients who suffered strokes had a mutation in the blood coagulation pathway.
Another finding was that they efficiently metabolised the micronutrient selenium. They also have genes that help in keeping blood pressure low. Wonkam added that selenium supplementation is worth investigating.
The study also found some patients were protected from some of the vascular complications of the disease by their ability to produce an amino acid called glutamine. Glutamine helps to protect the body against stress caused by low oxygen levels, which is one of the side-effects of SCA. This ability to produce glutamine can also be studied further as a possible treatment in other people with the disorder.
“It is possible that genes with recurrent mutations we found in numerous patients provide some protection, and have become prevalent in people with SCA by natural selection,” said the Director.
He said this information can be used in future in gene-modifying therapy. Modifier genes, which change the actions of other genes, can be beneficial to the health of the patients by countering some of the negative effects of the disorder.
“By identifying novel modifier genes, our research is providing additional mechanisms to explain the long-term survival or complications such as stroke in some patients. I believe this is probably one of the landmark findings performed in Africa, where most of these patients live,” he concluded.
