Increased Morbidity Risks Seen for Male, Female p.C282Y Homozygotes

WEDNESDAY, March 27, 2024 (HealthDay News) — Male and female p.C282Y homozygotes, including those undiagnosed with hemochromatosis, have increased morbidity risks, according to a study published in the March issue of BMJ Open.

Mitchell R. Lucas, from the University of Exeter in the United Kingdom, and colleagues conducted a prospective cohort study in the U.K. Biobank (2006 to 2010) involving 451,270 participants who were genetically similar to the 1,000 Genomes European reference population. Incident clinical outcomes and mortality were compared for those with HFE p.C282Y/p.H63D mutations and those without variants.

Overall, 12.1 percent of p.C282Y+/+ men had baseline hemochromatosis diagnoses; at 80 years, the cumulative incidence was 56.4 percent. The researchers found that 33.1 percent with and 25.4 percent without HFE variants died (hazard ratio, 1.29); joint replacements occurred in 27.9 and 17.1 percent, respectively; and liver disease occurred in 20.3 and 8.3 percent, respectively. Excess delirium, dementia, and Parkinson disease, but not depression, were observed. The group undiagnosed with hemochromatosis had similar associations, including excess mortality. Overall, 3.4 percent of p.C282Y+/+ women had baseline hemochromatosis diagnoses; at 80 years, the cumulative incidence was 40.5 percent. Excess incident liver disease (8.9 versus 6.8 percent; hazard ratio, 1.62), joint replacements, and delirium were present, with similar results seen for the undiagnosed group. No statistically significant excess fatigue or depression was seen at baseline for p.C282Y/p.H63D and p.H63D+/+ men or women, and they had no excess incident outcomes.

“Trials of targeted or community genotyping to diagnose haemochromatosis earlier appear justified, especially to identify people with the p.C282Y homozygote variants,” the authors write.

Abstract/Full Text