Having two copies of a common gene variant linked to iron metabolism increases a man’s risk for dementia more than two-fold, according to Australian research.
Notably, this association occurred in men but not in women, show study results published in the journal Neurology.
The homeostatic iron regulator (HFE) gene regulates iron metabolism in the body and mutations in this gene are known to cause hemochromatosis—a genetic condition that leads to excess iron buildup around the body.
Two mutations in HFE known as C282Y and H63D are known to cause differing levels of iron overload in the body and have also been suggested to increase the risk for dementia.
In this study, lead investigator John Olynyk, MD, a professor from Curtin Medical School in Australia, and colleagues assessed links between these two gene variants and dementia in a cohort of 12,174 individuals of European ancestry aged 70 years or older (54% women). These individuals were participants in another trial called the Aspirin in Reducing Events in the Elderly trial carried out in the U.S. and Australia.
The researchers looked at iron levels in controls and people who carried one or more of the two variants. Levels were highest in both men and women who were homozygous for one or both of the C282Y and H63D variants.
Iron levels alone did not appear to influence dementia risk, but men who were homozygous for the H63D variant had 2.39-fold higher dementia risk than those without either HFE variant. No link between this genotype and dementia risk was seen in women.
“The HFE gene is routinely tested for in most Western countries including Australia when assessing people for hemochromatosis—a disorder that causes the body to absorb too much iron. Our findings suggest that perhaps this testing could be offered to men more broadly,” said Olynyk in a press statement.
The lack of a connection between iron levels and dementia risk is interesting, notes Olynk. “This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body.”
The researchers now plan to investigate the mechanisms behind the higher risk for dementia in men with both copies of the H63D variant.
“While the genetic variant itself cannot be changed, the brain pathways which it affects— leading to the damage that causes dementia—could potentially be treated if we understood more about it,” said Olynyk.
