Hemochromatosis (HFE) genotype and atherosclerosis: Increased susceptibility to iron-induced vascular damage in C282Y carriers?

Abstract

Background The C282Y mutation of the hemochromatosis (HFE)-gene increases body iron status. Among Caucasians, the carrier frequency of this mutation is 8–9%. C282Y carriers may be more susceptible to iron-induced atherosclerosis due to higher iron levels. It has also been postulated that the C282Y mutation could alter aspects of iron metabolism. We examined the relationship between the C282Y mutation, iron status, and carotid intima-media thickness (IMT) as a marker of atherosclerosis. Methods and results The present study comprised 764 Dutch men and post-menopausal women aged 50–70 years. Mean and maximum carotid IMT were assessed by B-mode ultrasonography. Blood was sampled for assessment of the C282Y mutation and body iron status. Parameters of iron status (e.g. ferritin and non-transferrin bound iron) were significantly higher in C282Y carriers ( n = 80; 10%) compared to non-carriers ( P-values <0.001), however, there was no difference in the carotid IMT measures. Among non-smokers ( n = 222), carotid IMT was 0.051 mm (95% CI: 0.005; 0.096) lower in carriers compared to non-carriers ( P = 0.03), which remained after adjustment for iron parameters. Within the subgroup of carriers, higher carotid IMT values were observed across sex-specific quartiles of ferritin (mean IMT: 0.789, 0.787, 0.814, and 0.865 mm; P-trend = 0.08), whereas this association was absent in non-carriers. Conclusion Overall, we found no association of HFE genotype with carotid IMT, despite higher iron status. Interestingly, C282Y carriers may be hyper responsive to vascular damage which needs to be confirmed in prospective cohort studies.