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Evidence of Genetic Transmission in African Iron Overload
Victor M. Moyo,
Eberhard Mandishona,
Sandra J. Hasstedt,
Innocent
T. Gangaidzo,
Zvenyika A.R. Gomo,
Hlosukwazi Khumalo,
Thokozile Saungweme,
Clement F. Kiire,
Alan C. Paterson,
Peter Bloom,
A. Patrick MacPhail,
Tracey Rouault, and
Victor R. Gordeuk
From the Departments of Medicine and Chemical Pathology and the
Clinical Epidemiology Unit, University of Zimbabwe School of Medicine,
Harare, Zimbabwe; Departments of Medicine and Anatomical Pathology,
University of the Witwatersrand, Johannesburg, South Africa; Department
of Human Genetics, University of Utah Medical Center, Salt Lake City,
UT; Ormskirk and District General Hospital, Ormskirk, Lancashire,
England; Cell Biology and Metabolism Branch, National Institute of
Child Health and Human Development, Bethesda, MD; and Department of
Medicine, The George Washington University Medical Center, Washington,
DC.
Iron overload in Africa was previously regarded as purely due to
excessive iron in traditional beer, but we recently found evidence that
transferrin saturation and unsaturated iron binding capacity may be
influenced by an interaction between dietary iron content and a gene
distinct from any HLA-linked locus. To determine if serum ferritin
follows a genetic pattern and to confirm our previous observations, we
studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was
characterized with repeated morning measurements of serum ferritin,
transferrin saturation, and unsaturated iron binding capacity after
supplementation with vitamin C. For each measure of iron
status, segregation analysis was consistent with an interaction between
a postulated iron-loading gene and dietary iron content
(P < .01). In the most likely model, transferrin saturation
is 75% and serum ferritin is 985 µg/L in a 40-year-old male
heterozygote with an estimated beer consumption of 10,000 L, whereas
the saturation is 36% and serum ferritin is 233 µg/L in an
unaffected individual with identical age, sex, and beer consumption.
This segregation analysis provides further evidence for a genetic
influence on iron overload in Africans.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1076-1082
© 1998 by The American Society of Hematology.
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