Objective: To investigate the prevalence in the Michigan non-Hispanic Caucasian population of the C282Y, H63D and S65C mutations in the HFE gene associated with hereditary hemochromatosis. Methods: Polymerase chain reaction and restriction fragment length polymorphism analysis were performed on 3,532 blood samples from newborn screening cards provided by the state of Michigan. Results: More than 30% of Michigan Caucasians carry one HFE mutation, while 6% have two mutations. The allele frequency of the C282Y mutation is 5.7%, significantly higher than expected (p < 0.05), while the frequency of the H63D mutation is 14%, significantly lower than expected (p < 0.01). Conclusions: This is the first publication to examine HFE allele frequencies in an unbiased sample of the Caucasian population. Results indicate that the C282Y mutation may be more common in the non-Hispanic Caucasian population than previously reported, and medical problems related to iron overload may be a health concern for Michigan non-Hispanic Caucasians. Additional studies of penetrance for the C282Y allele are required to fully understand the impact of this information.

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