PredictingC282YHomozygote Genotype for Hemochromatosis Using Serum Ferritin and Transferrin Saturation Values from 44,809 Participants of the HEIRS Study

Abstract

INTRODUCTION: The simultaneous interpretation of serum ferritin level and transferrin saturation has been used as a clinical guide to diagnose genetic hemochromatosis. The Hemochromatosis and Iron Overload Screening (HEIRS) Study screened 101,168 North American participants for serum ferritin level and transferrin saturation, andC282Ygenotyping for theHFEgene.METHODS: Logistic regression involving a subsample of Caucasians (n=44,809) was used to predict individual probabilities ofHFE C282Yhomozygosity using serum ferritin and transferrin saturation values. Men (n=17,323) and women (n=27,486) were analyzed separately. Regression equations were evaluated using area under the curve from ROC analysis and variance explained by Nagelkerke’s pseudo R-squared. An Android smartphone App and website application were developed to provide physicians with easy access to predictingC282Yhomozygosity of theHFEgene.RESULTS: The logistic equation had an area under the ROC curve of 0.91 for men and 0.89 for women. The pseudo R-squared was 0.44 for men and 0.34 for women. An example analysis was a Caucasian man with a transferrin saturation of 50% and a ferritin level of 500 µg/L, who had a 1.3% (95% CI 1.1% to 8.8%) probability of being aC282Yhomozygote.CONCLUSIONS: A large primary care-based sample of 44,809 participants contributed to the development of a new computer/smartphone tool that predicts the probability of being aC282Yhomozygote of theHFEgene from serum ferritin and transferrin saturation values.