Elevated body iron stores are associated with morbidity and mortality due to 
oxidative stress. Hereditary hemochromatosis, a common condition caused by HFE 
gene mutations, can lead to excess iron storage and disease but clinical 
penetrance of HFE gene mutations is low and many people with elevated iron 
stores lack HFE mutations. We analyzed data from the Hemochromatosis and Iron 
Overload Screening Study to assess the relationship among HFE genotype 
(individuals with either homozygous or compound heterozygous status for C282Y 
and/or H63D HFE mutations were defined as genotype positive, or G+), elevated 
iron phenotype (individuals exceeding gender-specific transferrin saturation and 
serum ferritin threshold levels were considered phenotype positive, or P+), and 
leukocyte telomere length, a marker of biological aging and cumulative oxidative 
stress. In unadjusted analyses in comparison to individuals who were G-P-, G+P- 
were not significantly different (OR 0.74; 95% CI 0.26-2.04), while the G+P+ (OR 
2.03; 95% CI 1.15-3.56), and G-P+ (OR 2.24; 95% CI 1.5-3.29) had increased risk 
of short telomeres (<=25th percentile) rather than long telomeres (>=75th 
percentile). In analyses adjusting for age, gender, and race/ethnicity, the 
effect of individuals with elevated iron phenotypes having short telomeres 
persisted with G+P+ individuals (OR 1.94; 95% CI 1.02-3.72), and G-P+ 
individuals (OR 2.17; 95% CI 1.39-3.39) being significantly different from the 
G-P- group. In conclusion, elevated iron phenotype, but not HFE genotype, was 
associated with shortened telomeres. Further studies will be needed to determine 
whether telomere length provides a marker for morbidities specifically 
associated with iron overload.