Frequencies of C282Y and H63D alleles in the HFE gene among various Jewish ethnic groups in Israel: A change of concept required

Abstract

PurposeHereditary hemochromatosis has not been fully evaluated in the non-Ashkenazi population and is considered to be relatively rare. After ascertaining three unrelated hereditary hemochromatosis families of North African Jewish origin with the HFE C282Y/C282Y genotype, we evaluated the C282Y and H63D allele frequencies among the different Jewish ethnic groups in Israel, in particular North African Jews. MethodsData were collected from three Israeli Medical Centers. North African, Oriental, Yemenite, and Sephardic Jewish healthy individuals were assessed for the C282Y and H63D alleles. ResultsThe C282Y allele frequency was 1.02% (6/586 chromosomes), and the H63D allele frequency was 13.82% (81/586 chromosomes) in the North African Jewish group. The C282Y allele was not detected in the other non-Ashkenazi groups. The H63D allele frequency was 12.5% (38/304 chromosomes) in Oriental Jews, 14.9% (14/94 chromosomes) in Yemenite Jews, and 9.3% (11/118 chromosomes) in Sephardic Jews. DiscussionHereditary hemochromatosis is underrecognized among North African Jews, who have carrier frequencies of 1/58 and 1/4 for C282Y and H63D, respectively. HFE-hereditary hemochromatosis is not rare among this population as currently thought and merits increased awareness to prevent endpoint disease. The frequent occurrence of β-thalassemia trait and HFE-H63D in non-Ashkenazi Jews raises the possibility of genetic interactions contributing to iron overload when coinherited and requires further evaluation.