Australian researchers have identified a common genetic variant that significantly increases the risk of dementia in men, potentially paving the way for more personalised approaches to prevention and treatment.
The research team from Curtin University found that a variant of the HFE gene, known as H63D, is carried by approximately one in three people in a single copy and by one in 36 in a double-copy form.
Published in the journal Neurology, the study revealed that men who carry two copies of the H63D variant are more than twice as likely to develop dementia in their lifetime compared to women with the same genetic profile.
The study analysed data from 19,114 healthy older adults across Australia and the United States to determine whether mutations in the HFE gene—which regulates iron levels in the body—could influence dementia risk.
“Having just one copy of this gene variant does not impact a person’s health or increase their risk of dementia. However, having two copies more than doubled the risk of dementia in men, but not in women,” said Professor John Olynyk from the Curtin Medical School.
While the gene itself cannot be altered, Olynyk said the brain pathways it affects—and which ultimately cause damage leading to dementia—could be targets for future treatment.
The reason why this variant affects men more than women remains unclear. “Further research is needed to understand why this genetic variant increases dementia risk specifically in males,” Olynyk added.
The HFE gene is commonly tested in Western countries, including Australia, when screening for hemochromatosis—a disorder where the body absorbs too much iron. The researchers suggest that broader screening, especially for men, could be considered in light of these findings.
Interestingly, although the HFE gene influences iron regulation, the team found no direct link between elevated iron levels in the blood and dementia risk among men with the variant.
“This suggests other mechanisms may be involved, possibly including increased inflammation and cell damage in the brain,” Olynyk noted.
The findings offer promising insights into more targeted dementia prevention strategies and highlight the need for gender-specific research in understanding the genetic underpinnings of neurodegenerative diseases.
—IANS
