(P10-003-23) Characterization of Iron Status Biomarkers and Regulatory Hormones Among East Asian and European Adults

Objectives: Risk of excess body iron (Fe) differs between populations and is associated with adverse health outcomes. The highest risk of elevated serum ferritin (SF) is observed in adults (median age 50 y) with self-reported East Asian (EA) ancestry compared to other populations despite having the lowest frequency of the hemochromatosis mutation (C282Y) which is most prevalent in Northern Europeans (EU). Our aims were to characterize and compare Fe status markers [SF, hemoglobin (Hb)], regulatory hormones [hepcidin (Hep), erythroferrone (ERFE), erythropoietin (EPO)] and ratios between these markers in EA and EU adults.

Methods: Participants were non-smoker men (n=137) and women (n=211) of EA (n=168) and EU (n=180) descent aged 18-50 y without obesity or other chronic diseases. Females were pre-menopausal, not pregnant or lactating. Fasting ( >2h) blood samples were collected. Hb (g/dL) was measured on a hematology analyzer, SF (µg/L) was measured using an immunoassay, and Hep (ng/mL), ERFE (ng/mL), and EPO (mIU/mL) were measured by ELISA. Ancestry was genetically verified using genotyping data from the Illumina Global Diversity Array. Mann Whitney U test was used to evaluate differences between ancestry groups. Results are reported as median [IQR].

Results: Among EA participants 59% were females and among EU participants 63% were females (P=0.4). Median age was 22.0 [6.0] y in EA and 26.9 [15.0] y in EU participants (P < 0.01). SF was higher in EA (76.0 [119]) compared to EU (51.1 [64.5]) participants (P < 0.01). Hb did not differ between ancestry groups (EA: 13.8 [2.0], EU: 13.7 [1.8]; P=0.6). With respect to regulatory hormones, Hep and ERFE were higher in EA (Hep: 28.2 [33.7]; ERFE: 0.3 [2.2]) compared to EU (Hep: 24.4 [20.3]; ERFE: 0.08 [0.6]) participants (all P < 0.05), but EPO did not differ between ancestry groups (EA: 6.9 [4.8], EU: 7.5 [3.4]; P=0.1). The Hb:SF and Hep:SF ratios were lower and the Hep:EPO and ERFE:EPO ratios higher in EA compared to EU participants (all P < 0.05).

Conclusions: Significantly higher Fe stores are evident in young adults of EA compared to EU ancestry. Hormonal differences suggest altered regulation of Fe utilization between these ancestry groups. These results highlight the need for a greater understanding of ancestry-driven differences in accumulation of nutrients like Fe that are universally supplemented at key life stages.

Funding Sources: NIH, AHA