Transferrin Saturation and Mortality

Abstract

To the Editor: Ellervik and colleagues (1) recently reported a positive association between transferrin saturation (TS) and mortality. Several questions arise from this observation: Is the association due to all causes of iron overload or to hereditary hemochromatosis only? Does the study underestimate the true association? And, is mortality due to variation in iron, transferrin, or both? We have relevant data from population-based studies of twins and families of European descent living in Australia (2, 3). TS values (calculated from serum transferrin and iron) and HFE (hemochromatosis) genotypes for C282Y (rs1800562, genotyped) and H63D (rs1799945, imputed) are available for 8096 adults (3151 men and 4945 women; mean age, 47 years). Replicate TS measurements are available for 460 participants (178 men and 282 women) from studies in 1993–1996 and 2001–2005. Their mean age at the time of the second study was 50 years (range, 39–72 years). The Discussion in the Ellervik et al. report implies that the association of TS with mortality is driven by the C282Y variant (which is associated with …