While most of us carry the same human genes, those genes can have small changes or variations in their sequences, which can have a wide range of effects; some genetic changes may have very little or no effect on biology, others can have huge ramifications. Scientists have already revealed a lot about specific genetic mutations or variants that cause disease, while we are still learning about genetic variants that influence a carrier's risk of disease. This is a complex situation as well, where multiple variants can have different or additive effects.
Scientists have now identified a genetic variant that causes male carriers to be twice as likely to develop dementia at some point in their lifetime, compared to non-carriers. In this work, the scientists analyzed a huge amount of health and genetic data from the ASPirin in Reducing Events in the Elderly (ASPREE) to find genetic variants in the hemochromatosis (HFE) gene, and determine if they are associated with dementia. This trial was intended primarily to assess the effects of aspirin intake, but it also collected a wealth of health data on over 19,000 individuals.
This gene encodes for a protein that helps control the levels of iron in the body. The findings showed that one in three individuals carry one copy of a HFS variant called H63D, and one in 36 individuals carry two copies of this variant. Men who carry two copies of this variant are more than twice as likely to develop dementia, but this was not true for women who carried two copies. The findings have been reported in Neuron.
"Having just one copy of this gene variant does not impact someone's health or increase their risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not women," noted study co-author Professor John Olynyk of the Curtin Medical School.
More research will be needed to determine exactly why this genetic variant has this effect in men. But learning more about the gene and the biochemical pathways that it's related to may help us learn more about dementia, and potentially, how to treat it, added Olynyk.
"While the HFE gene is critical for controlling iron levels in the body, we found no direct link between iron levels in the blood and increased dementia risk in affected men," added Olynyk. "This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body."
Many countries perform HFE gene testing because mutations in the disorder can cause hemochromatosis, in which the body takes up excessive amounts of iron. "Our findings suggest that perhaps this testing could be offered to men more broadly," Olynyk said.
Sources: Curtin University, Neuron