Research conducted by the Research Centre for Optimal Health at the University of Westminster in collaboration with Calico Life Sciences LLC has found that spleen iron accumulation is linked to two genes called ANK1 and SPTA1 which are involved in ‘hereditary spherocytosis’, a condition which affects red blood cells.
It has not previously been clearly understood why patients with mutations in genes linked to hereditary spherocytosis have so much variation in their disease severity. Through the researchers’ work, they have identified common genetic variants which may modify the effect of rare alternative forms of genes which are known to cause disease. This may explain why some people are more significantly affected by the disease.
The researchers’ observations must be replicated in further disease cohorts; however, this first-of-its-kind research could be a pivotal step to predict disease severity and could be used to clinically characterise hemolytic anemia, a red blood disease disorder.
In the study, the researchers used magnetic resonance imaging (MRI) to measure how much iron is stored in the spleen which is the largest filter of blood in the human body. They found that spleen iron accumulation links to ANK1 and SPTA1 - mutation in these genes sometimes causes hereditary spherocytosis. Their data suggests that these variants result in a low turnover of long-lived red blood cells and therefore result in higher levels of spleen iron, since the spleen in responsible for removing and recycling them from the blood.
They found that a small proportion of the population had elevated spleen iron (1.04%), with some having pathologically high levels of iron accumulation (0.32%). Accordingly, they proposed a reference range for spleen iron in an adult population of 0.54 – 1.69 milligrams per gram (mg/g). Spleen iron was generally higher in men and increased with advancing age. For women, the increase happened after menopause. Elevated levels were also found to be related to diet, particularly red meat intake.
Previous studies on spleen iron have typically had small sample numbers of specific disease groups, however the researchers were able to measure spleen iron in 41,764 participants from the UK Biobank, making it the largest study of its kind. The team have also run genome-wide association studies which have allowed them to identify the genes involved in the regulation of spleen iron.
Talking about the study, Dr Nicolas Basty, Joint Lead Researcher and Research Fellow at the University of Westminster, said: “UK Biobank participants are very generous with their time, spending several hours travelling to the centres in order to undergo several scans, all for the greater good and no financial incentive or benefit to themselves. I think it is important to appreciate the sacrifice the volunteers are making and therefore we need to do our best to maximise data usage.
“In addition to ensuring all acquired images are analysed, we also need to look at the data in new ways. Medical images often contain other structures within their field of view, in addition to those targeted. For example, here we are dealing with liver images, which we were able to reuse to make clinically relevant measurements of the spleen. I am very happy to see how far this vision has gone, and the study perfectly sums up our interdisciplinary collaboration with Calico.”
Dr Elena Sorokin, First Author and Joint Lead Researcher from Calico Life Sciences LLC, added: “This work illustrates the power of modern imaging techniques to non-invasively measure organ and tissue physiology and creates an exciting opportunity for interdisciplinary collaboration between imaging scientists and computational geneticists. By measuring spleen iron in a population-based cohort, we were able to identify genetic factors linked to the red blood cell life cycle and homeostasis.”
Find out more about research at the University of Westminster.
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