Gene involved in haemoglobin control found in genome-wide association study

Research lead

A gene with a significant role in regulating haemoglobin has been identified as part of a genome-wide association study looking at the link between genes and haemoglobin levels in 16,000 people. The research, carried out by scientists from Imperial College London, shows a strong association between the gene, TMPRSS6, and the regulation of haemoglobin.

“Understanding how haemoglobin levels are controlled at a genetic level has significant public health implications for people of all ages,” said John Chambers, from the Department of Epidemiology and Public Health at Imperial and one of the lead researchers.

Problems with haemoglobin production affect the oxygen-carrying capacity of the blood causing common diseases, such as anaemia, which affects some 25 per cent of the world's population.

Abnormally high or low levels of haemoglobin are associated with a range of serious health problems, such as poor growth (low levels) and increased risk of stroke (high levels). Changes in hemoglobin levels can also affect susceptibility to diseases like malaria.

The researchers say their findings adds to understanding of the multiple causes of problems with haemoglobin levels, which include an iron-deficient diet, chronic diseases such as cancer, and genetic associations, such as the one described in this paper. In the future, the finding could lead to new treatments for people suffering from chronic problems with haemoglobin levels that are not linked to iron in the diet.

The enzyme protein produced by the TMPRSS6 gene is a good target for drug development. Designing a drug that enhances TMPRSS6 activity could augment haemoglobin in people such as cancer and kidney failure patients, who suffer from chronically low levels,” said Chambers.

The research is one of a series of new findings on links between genes and regulation of blood cell characteristics. The Imperial research focuses on two unique aspects in particular. First, the genomic analysis is based on individuals of European and Indian Asian ancestry, and shows a strong link in both populations, emphasising the global relevance of the finding, by showing it is not confined to individual ancestries.

Second, the paper includes evidence for how the genetic variant affects TMPRSS6 function at a molecular level, and shows that the genetic variation causes an amino acid change near the enzyme’s active site, that is likely to affects the way TMPRSS6 reacts with target molecules.