Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2175-2179
Distribution of Transferrin Saturations in the African-American
Population
By
Victor R. Gordeuk,
Christine E. McLaren,
Anne C. Looker,
Victor Hasselblad, and
Gary M. Brittenham
From the Department of Medicine, The George Washington University
Medical Center, Washington D.C.; the Department of Mathematics,
Moorhead State University, Moorhead MN; the Nutrition Statistics
Branch, National Center for Health Statistics, Hyattsville MD; the
Center for Health Policy Research and Education, Duke University,
Durham, NC; and the Department of Medicine, MetroHealth Medical Center,
Case Western Reserve University School of Medicine, Cleveland OH.
 |
ABSTRACT |
To determine if transferrin saturations in African Americans may
reflect the presence of a gene that influences iron metabolism, we
analyzed the distribution of these values in 808 African Americans from
the second National Health and Nutrition Survey. We tested for a
mixture of three normal distributions consistent with population genetics for a major locus effect in which the proportion of normal homozygotes is p2; of heterozygotes, 2pq;
of affected homozygotes, q2; and in which p+q
= 1. Three subpopulations based on transferrin saturation were
present (P < .0001) and the fit to a mixture of three normal
distributions was good (P = .2). A proportion of .009 was
included in a subpopulation with a mean ± standard deviation transferrin saturation of 63.4% ± 5.7% (postulated
homozygotes for a gene that influences iron metabolism), while a
proportion of .136 had an intermediate saturation of 38.0% ± 5.7%
(postulated heterozygotes) and .856 a saturation of 24.6% ± 5.7%
(postulated normal homozygotes). These proportions were consistent with
population genetics because the sum of the square roots of the
proportions with the lowest mean transferrin saturation (P = .925) and the highest (q = 0.093) was approximately 1 (1.018). The results are consistent with the presence in African
Americans of a common locus that influences iron metabolism.
| |
INTRODUCTION |
IRON OVERLOAD IS COMMON in
Africa,1 but this condition is not widely considered to be
a problem among African Americans whose ancestors originated in Africa.
Recognized for more than 60 years,2 iron overload in Africa
is etiologically related to increased dietary iron.3 A
recent study suggested that a non-HLA-linked iron-loading gene may
also be implicated in the pathogenesis, with heterozygotes for the
iron-loading locus developing iron overload only in the face of high
dietary iron, but with homozygotes becoming iron-loaded even without
increased dietary iron.4
In the United States, primary iron overload is regarded as
predominantly a problem among Caucasian Americans in the form of HLA-linked hemochromatosis. Based on screening the population for
homozygotes, the estimated gene frequency for this recessive disorder
is .067.5 Recently, we used a novel application of statistical mixture modeling to analyze the distribution of transferrin saturations in white Americans and to estimate the prevalence of
hemochromatosis heterozygotes in that population. Our findings were
consistent with a distinct distribution of transferrin saturations in
hemochromatosis heterozygotes and with a gene frequency of .07 to
.08.6
The present study was prompted by a concern that a primary iron
overload condition may be present in the African-American population,
but be largely unrecognized and untreated. We postulated that, in an
analogous situation to that of HLA-linked hemochromatosis in whites, an
iron-loading locus in African Americans might be manifested by
distinct, statistically discernible subpopulations in the distribution
of population transferrin saturation data.
| |
MATERIALS AND METHODS |
Source of data.
The second National Health and Nutrition Examination Survey, which
studied a representative sample of the noninstitutionalized United
States population ages 6 months to 74 years from 1976 to 1980, was the
source of data for the present study. In this survey, 20,322 persons
were examined from 64 primary sampling units (counties or small groups
of contiguous counties). Based on an interviewer's observation, each
person was classified as white, black, or other. Of those surveyed,
2,763 (13.6%) were African Americans. Serum iron and total iron
binding capacity were measured by a modification of the Automated
Technicon AAII-25 method, which is a colorometric method using
ferrozine; the transferrin saturation was calculated from these values
by dividing the serum iron by the total iron binding capacity and
multiplying by 100.7,8
Selection criteria.
We selected transferrin saturations from African-American men and women
aged 20 years to 74 years for whom the mean corpuscular volume was
between 80 fL and 100 fL and the erythrocyte protoporphyrin was < 70 mg/dL red blood cells. Additional selection criteria included
hemoglobin concentration 
13.5 g/dL and hematocrit 40% for men and
hemoglobin 11.5 g/dL and hematocrit 34% for women. We excluded
subjects with abnormally low hemoglobin or hematocrit values because
anemias of various causes are associated with abnormally high9-11 or low12-14 transferrin saturations.
We excluded subjects with abnormal values for mean corpuscular volume
because a low mean corpuscular volume can be associated with iron
deficiency or inflammation and a high mean corpuscular volume can be
associated with megaloblastic conditions and drug
effects,14 all of which can lead to altered transferrin
saturations.12,13,15,16 We excluded subjects with elevated
erythrocyte protoporphyrin levels because of the associations with iron
deficiency and inflammation.9,17 After applying the
selection criteria, there were 836 individuals in the data set. As
described later, an additional 28 subjects were excluded as possible
heterozygotes for HLA-linked hemochromatosis. Table 1 gives the numbers of subjects
excluded using specific criteria.
Adjustment of transferrin saturations for gender and diurnal
variation.
Because transferrin saturation has a diurnal
variation,15,18 the inclusion of samples obtained at
different times of the day, without appropriate adjustment, in an
analysis of distribution might alter the results. In addition, because
of the relatively small size of the sample data from men (368) and
women (468), analyzing the individual distributions could result in
inappropriately large standard errors for parameter estimates. In this
study, we adjusted transferrin saturation values for blood samples
drawn in the afternoon or evening to reflect expected values had the blood samples been drawn in the morning. These expected values were
determined using linear regression analysis in the following manner.
First, for each gender, the transferrin saturation values were
stratified by time of blood collection (morning, afternoon, or evening)
and each stratum was divided into deciles. Second, a regression
equation was determined using the average value of transferrin
saturations for each decile from blood samples drawn in the morning as
the dependent variable. Predictors included an indicator variable for
gender and the average value of transferrin saturations by decile from
blood samples drawn in the afternoon. Similarly, a separate regression
equation was formed for use with transferrin saturation values from
blood samples drawn in the evening. Third, the predicted average
morning transferrin saturation value was then computed for samples
drawn in the afternoon or evening using the appropriate regression
equation. To form the frequency distributions of transferrin saturation
described below, all of the values for samples drawn in the morning and
the predicted morning values for samples drawn in the afternoon or
evening were used.
Adjustment of the data set to account for a possible admixture of
Caucasian HLA-linked hemochromatosis genes.
The data were modified to take into account the possibility that the
distribution of transferrin saturations from African Americans is
affected by individuals who are heterozygotes or homozygotes for
HLA-linked hemochromatosis. The gene frequency for the HLA-linked
hemochromatosis locus in the Caucasian population is estimated to be
.067.5 Assuming a 25% admixture of Caucasian genes in the
African-American population,19 the gene frequency for the
HLA-linked hemochromatosis locus in African Americans would be 25% of
.067 or .017. Population genetics would then project for African
Americans a proportion of homozygotes for the HLA-linked hemochromatosis gene of 3 per 10,000 (.017 squared) and a proportion of
heterozygotes of 33 per 1,000. We assumed that the transferrin saturation values from these projected African American heterozygotes for the HLA-linked hemochromatosis locus would be normally distributed with the same mean and SD as found in our previous study of Caucasian Americans in the second National Health and Nutrition Examination Survey (NHANES II).6 Under this assumption, we removed
3.3% of the 836 values (n = 28) from the data set that were closest to
28 random values generated from a normal distribution with a mean of
45.5% and a SD of 7%. In the case when several transferrin saturation
values were equidistant to a randomly generated value, one of these
values was selected randomly. Because the number of transferrin
saturations arising from homozygotes for HLA-linked hemochromatosis was
projected to be less than one, no further adjustment was made to the
data.
Distribution of transferrin saturation values in African Americans.
We examined the distributions of adjusted transferrin saturation values
for the remaining 808 men and women African Americans in the unweighted
data using techniques developed for the analysis of distributions in
grouped, truncated data.20 Transferrin saturation values
were sorted into intervals and the frequency of values within each
interval was computed. The physiologic models we considered were a
single normal distribution and a mixture of two or three normal
distributions. We have previously established that transferrin saturations in a homogeneous population follow a normal
distribution.6 The expectation-maximization algorithm was
applied to the distributions of transferrin saturation values for
parameter estimation.20,21 Equal variances were assumed for
fit to mixtures of normal distributions because models with unequal
variances resulted in increased variances for the subpopulation with
the highest transferrin saturation that were biologically implausible.
The statistical test used to determine the best fitting model was based
on the likelihood ratio statistic. For each observed distribution, the
maximized log-likelihood function for a mixture of three normal
distributions was evaluated (Log L1) and compared with the
maximized log-likelihood function (Log L0) for either a single
normal distribution or a mixture of two normal distributions.
Significance of the likelihood ratio statistic,
-2[Log(L0/L1)], was assessed by referring to the
2 distribution with degrees of freedom based on the
difference between the number of parameters being estimated under each
model. A significance level of .05 was used. Similarly, the maximized log-likelihood function for a mixture of three normal distributions was
compared with that of a single normal distribution and to that of two
normal distributions. The 2 statistic was then used to
test goodness of fit of each observed distribution to the best fitting
model. For the three-population model, the methods of Crump and
Howe22 were used to compute confidence intervals for the
proportion with the highest mean.
Weighting the results to reflect the African-American population as
a whole.
The assumptions underlying our analysis were that transferrin
saturation values are independent and identically distributed, ie, each
observation has an equal chance of being selected, and that all
observations come from the same distribution. However, because
individuals in the NHANES II sample did not have an equal probability
of selection, sample weights must be used to calculate parameter
estimates that reflect the United States population. For NHANES II, a
multistage estimation procedure was used to calculate sample weights so
that point estimates would reflect the United States
population.8,23 The methods described above were used to
compute parameter estimates from the weighted transferrin saturation distribution to reflect results for African-American men and women in
the United States population fitting our exclusion criteria. It was not
possible to adjust the variance estimates to account for the complex
design of NHANES II.
Estimation of gene frequency for a possible locus that influences
iron status in African Americans.
Accepting the possibility that our findings might represent the
presence of a locus that influences iron metabolism among African
Americans, we assumed that the three normal distributions of
transferrin saturation in our analyses would represent predominantly a
subpopulation of normal homozygotes, a subpopulation of heterozygotes, and a subpopulation of affected homozygotes. We estimated the proportions of normal homozygotes, heterozygotes, and affected homozygotes as the proportions in the populations with the lowest, intermediate, and highest mean transferrin saturations, respectively. According to the Hardy-Weinberg equilibrium equation,
p2 (the proportion of normal homozygotes) + 2pq (the proportion of heterozygotes) + q2
(the proportion of abnormal homozygotes) = 1. We estimated the gene
frequency of the abnormal allele (q) as the square root of the
proportion from the population with the highest mean transferrin saturation. We estimated the gene frequency of the normal homozygotes (p) as the square root of the proportion from the population
with the lowest mean transferrin saturation. We then examined whether the modeled distributions were consistent with population genetics for
a major locus effect in which p + q = 1.
| |
RESULTS |
Analysis of unweighted data.
The primary analysis was performed on transferrin saturations for 808 individuals. The transferrin saturations had been adjusted for sex and
diurnal variation and the data set had been adjusted for the possible
presence of an HLA-linked hemochromatosis allele as described above.
The unweighted data showed a significantly better fit to three normal
populations than to two normal populations (likelihood ratio statistic,
32.1 with 3 degrees of freedom; P < .0001) or to a single
normal population (likelihood ratio statistic 123.1 with 7 degrees of
freedom, P < .0001). The fit of the data to a mixture of
three normal populations was good (P = .20; in a
goodness-of-fit analysis, a P value above .1 indicates an
acceptable fit). Figure 1A shows the
observed and fitted distributions for unweighted transferrin saturation
values. An estimated proportion of .856 of the African Americans
studied were included in a subpopulation with a mean saturation of
24.6%, while .135 comprised a subpopulation with an intermediate mean
saturation of 38.0% and .009 (95% confidence interval of .004 to
.017) formed a subpopulation with a mean saturation of 63.4%
(Table 2). These proportions
are consistent with population genetics for a single major locus
affecting the distribution of transferrin saturations: the sum of the
square roots of the proportion with the lowest transferrin saturation
(P = .925) and of the proportion with the highest saturation
(q = .093) is approximately 1 (1.018).
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| Fig 1.
Distribution of transferrin saturation values in African
Americans. The interval width is 3%. (A) Original sample of 808 values. (B) Weighted data for the African American population. The
dashed lines represent the fitted normal distributions representing
three subpopulations. The overall fitted mixture distribution is shown with a solid line.
|
|
Weighted results for the African American population.
The results after the data (adjusted for sex, diurnal variation, and
the potential presence of HLA-linked hemochromatosis) were weighted to
reflect the United States population of African Americans as a whole
are given in Table 2. The weighted results are similar to
our primary results using unweighted data, which suggests that the
unequal probability of selection in NHANES II did not have a major
input on the transferrin saturation distribution. An estimated
proportion of .815 was included in a subpopulation with a mean
saturation of 24.3%, while .172 comprised a subpopulation with an
intermediate mean saturation of 39.1% and .012 formed a subpopulation
with a mean saturation of 61.0%. The weighted findings are also
consistent with population genetics for a single major locus affecting
the distribution of transferrin saturations: the sum of the square
roots of the proportion with the lowest transferrin saturation
(P = .903) and of the proportion with the highest
saturation (q = .112) is approximately 1 (1.015).
| |
DISCUSSION |
Our analysis of transferrin saturations from African Americans studied
in the second National Health and Nutrition Examination Survey showed
that three subpopulations of individuals could be detected. Using data
that were adjusted for the time of day of collection of the blood
sample, for gender, and for the possible presence of an HLA-linked
hemochromatosis allele, we found that one subpopulation comprised an
estimated proportion of .856 of the African Americans studied and had a
mean transferrin saturation of 24.6%. A second subpopulation was made
up of an estimated proportion of .136 and had a mean transferrin
saturation of 38.0%. A third subpopulation comprised a proportion of
.009 and had a mean transferrin saturation of 63.4%. Limitations to
this analysis are that transferrin saturations were single rather than
repeated determinations, that subjects were not screened for liver
diseases that may be associated with elevations of transferrin
saturation, and that the sample size was small for a population study.
In addition, we were not able to fully account for the complex survey
design when estimating variances.
The three subpopulations that we identified based on this
mixture-modeling statistical analysis of transferrin saturation data
from African Americans are consistent with the presence of a major
locus that influences iron status. If we assume that the members of the
small subpopulation with the highest mean transferrin saturation may be
abnormal homozygotes for a locus that influences iron metabolism, then
the abnormal gene frequency in this data set would be estimated to be
.093. Similarly, if we assume that the members of the large
subpopulation with the lowest mean transferrin saturation may be normal
homozygotes for a locus that influences iron metabolism, then the
normal gene frequency would be .925. Consistent with population
genetics for a single major locus, the sum of the estimated normal and
abnormal gene frequencies is approximately 1 (1.018).
If our present findings do reflect the presence in the African-American
population of an abnormality of a major locus that influences iron
metabolism, then this locus may be either (1) the HLA-linked
hemochromatosis gene that has heretofore been described exclusively in
people of European ancestry15,24 or (2) some different gene
that influences iron metabolism. The fact that HLA-linked
hemochromatosis has only been reported in Caucasians and that a genetic
iron-loading disorder that is not linked to the HLA-locus may be common
in Africa4 are supportive of the possibility that we are
observing the effects of a genetic alteration that is unique to people
of African ancestry. There is an admixture of Caucasian genes in the
African-American population, estimated to be about 25%,19
but such an admixture would not be sufficient to explain the findings
of the present study. The gene frequency of HLA-linked hemochromatosis
in the United States white population is estimated to be
.0675 and an estimated 25% admixture of Caucasian genes
could lead to an estimated gene frequency of only .017 for HLA-linked
hemochromatosis in the African-American population. Furthermore, we
made an adjustment to account for the probable presence of HLA-linked
hemochromatosis heterozygotes in the present study.
Until recently, only rare mention has been made in the literature of
African Americans with "hemochromatosis".25-29 Two
recent reports underscore the fact that primary iron overload does
occur among African Americans.30,31 Furthermore, one study
raises that possibility that the condition may not be
rare.31 The present statistical study of the distribution
of transferrin saturation values is compatible with the possibility
that an alteration in a gene that influences iron metabolism is present
among African Americans. Clinicians should consider the diagnosis of
primary iron overload in African-American patients and both treat the condition and screen family members of affected subjects.
Investigations to define the prevalence, clinical consequences, and
causes of primary iron overload in African Americans are needed.
| |
FOOTNOTES |
Submitted September 25, 1997;
accepted October 28, 1997.
Supported in part by a grant from the Office of Minority Health to the
Cell Biology and Metabolism Branch, National Institute of Child Health
and Human Development (Bethesda, MD) and by a grant from the National
Center for Health Statistics, Centers for Disease Control (Hyatsville,
MD).
Address reprint requests to Victor R. Gordeuk, MD, Suite 3-428, 2150 Pennsylvania Ave NW, Washington DC 20037.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
| |
REFERENCES |
1.
Gordeuk VR:
Hereditary and nutritional iron overload.
Balliere's Clin Haematol
5:169,
1992[Medline]
[Order article via Infotrieve]
2. Strachan AS: Haemosiderosis and Haemochromatosis in South African
Natives with a Comment on the Etiology of Haemochromatosis. MD Thesis,
University of Glasgow, Scotland, 1929
3.
Bothwell TH,
Seftel H,
Jacobs P,
Torrance JD,
Baumslag N:
Iron overload in Bantu subjects. Studies on the availability of iron in Bantu beer.
Am J Clin Nutr
14:47,
1964[Abstract/Free Full Text]
4.
Gordeuk V,
Mukiibi J,
Hasstedt SJ,
Samowitz W,
Edwards CQ,
West G,
Ndambire S,
Emmanual J,
Nkanza N,
Chapanduka Z,
Randall M,
Boone P,
Romano P,
Martell RW,
Yamashita T,
Effler P,
Brittenham G:
Iron overload in Africa. Interaction between a gene and dietary iron content.
N Engl J Med
326:95,
1992[Abstract]
5.
Edwards CQ,
Griffen LM,
Goldager D,
Drummond C,
Skolnick MH,
Kushner JP:
Prevalence of hemochrmatosis among 11,065 presumably healthy blood donors.
N Engl J Med
318:1355,
1988[Abstract]
6.
McLaren CE,
Gordeuk VR,
Looker AC,
Hasselbad V,
Edwards CQ,
Griffen LM,
Kushner JP,
Brittenham GM:
Prevalence of hemochromatosis heterozygotes in United States whites.
Blood
96:2021,
1995[Free Full Text]
7. Gunter EW, Turner WE, Nease JW, Bayse DD: Laboratory procedures
used by the Clinical Chemistry Division, Centers for Disease Control
for the Second Health and Nutrition Examination Survey (NHANES II)
1976-1980. U.S. Department of Health and Human Services, Public Health
Service, Centers for Disease Control, Center for Environmental Health,
Nutritional Biochemistry Branch, Atlanta, GA, 1981
8. Fulwood R, Johnson CL, Bryner JD, Gunter EW, McGrath CR:
Hematological and nutritional biochemistry reference data for persons 6 months - 74 years of age: United States, 1976-1980. DHHS Publication
No. (PHS) 83-1682. U.S. Department of Health and Human Services, Public
Health Service, National Center for Health Statistics, Hyattsville, MD,
December, 1982
9.
Cartwright GE,
Hughley CM,
Ashenbrucker H,
Faye J,
Wintrobe MM:
Studies on free erythrocyte proto-porphyrin, plasma iron and plama copper in normal and anemic subjects.
Blood
3:501,
1948[Abstract/Free Full Text]
10.
Finch CA,
Deubelbeiss K,
Cook JD,
Eschbach JW,
Harker LA,
Funk DD,
Marsaglia G,
Hillman RS,
Slichter S,
Adamson JW,
Ganzoni A,
Biblett ER:
Ferrokinetics in man.
Medicine
49:17,
1970[Medline]
[Order article via Infotrieve]
11.
Hershko C,
Graham G,
Bates GW,
Rachmilewitz EA:
Non-specific serum iron in thalassaemia: An abnormal serum fraction of potential toxicity.
Br J Haematol
40:255,
1978[Medline]
[Order article via Infotrieve]
12.
Cartwright GE,
Wintrobe MM:
Chemical, clinical, and immunological studies on the products of human plasma fractionation. XXXIX. The anemia of infection. Studies on the iron-binding capacity of serum.
J Clin Invest
28:86,
1949
13.
Bainton DF,
Finch CA:
The diagnosis of iron deficiency anemia.
Am J Med
37:62,
1964[Medline]
[Order article via Infotrieve]
14. Jandl JH: Blood. Boston, MA, Little, Brown, 1987
15.
Edwards CQ,
Griffen LM,
Kushner JP:
Twenty-four hour variation of transferrin saturation in treated and untreated hemochromatosis homozygotes.
J Intern Med
226:173,
1989
16.
Gordeuk VR,
Brittenham GM,
McLaren GD,
Spagnuolo PJ:
Hyperferremia in immunosuppressed patients with acute nonlymphocytic leukemia and the risk of infection.
J Lab Clin Med
108:466,
1986[Medline]
[Order article via Infotrieve]
17.
Devasthali SD,
Gordeuk VR,
Brittenham GM,
Bravo JR,
Hughes MA,
Keating LJ:
Bioavailability of carbonyl iron: A randomized, double-blind study.
Eur J Haematol
46:272,
1991[Medline]
[Order article via Infotrieve]
18.
Hamilton LD,
Gubler CJ,
Cartwright GE,
Wintrobe MM:
Diurnal variation in the plasma iron level of man.
Proc Soc Exp Biol Med
75:65,
1950
19.
Chakraboty R,
Kamboh MI,
Nwankwo M,
Ferrill RE:
Caucasian genes in American blacks: New data.
Am J Hum Genet
50:145,
1992[Medline]
[Order article via Infotrieve]
20. Hassselblad V: Manual for the Grouped DISFIT Software. Version
1.1. Durham, NC, Duke University, 1992
21.
Dempster AP,
Laird NM,
Rubin DB:
Maximum likelihood from incomplete data via the EM algorithm.
J Roy Stat Soc Series B
39:1,
1977
22. Crump, KS, Howe R: A preview of methods for calculating
confidence limits in low dose extrapolation, in Krewski D (ed):
Toxicological Risk Assessment. Boca Raton, FL, CRC, 1985, p 188
23. McDowell A, Engle A, Massey F, Maurer K: Plan and Operation of
the Second National Health and Nutrition Examination Survey, 1976-1980. Vital and Health Statistics. Series 1-No. 15. DHHS Publication No.
(PHS) 81-1317. US Department of Health and Human Services. Public
Health Service. Hyattsville, MD, National Center for Health Statistics,
July 1981
24.
Simon M,
Le Mignon L,
Fauchet R,
:
A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) Mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association.
Am J Hum Genet
41:89,
1987[Medline]
[Order article via Infotrieve]
25.
Krainin P,
Kahn BS:
Hemochromatosis: Report of a case in a Negro; discussion of iron metabolism.
Ann Intern Med
33:452,
1950
26.
MacDonald RA,
Mallory GK:
Hemochromatosis and hemosiderosis.
Arch Intern Med
105:686,
1960
27.
Rosner IA,
Askari AD,
McLaren GD,
Muir A:
Arthropathy, hypouricemia and normal serum iron studies in hereditary hemochromatosis.
Am J Med
70:870,
1981[Medline]
[Order article via Infotrieve]
28.
Muir WA,
McLaren GD,
Braun W,
Askari A:
Evidence for heterogeneity in hereditary hemochromatosis. Evaluation of 174 individuals in nine families.
Am J Med
76:806,
1984[Medline]
[Order article via Infotrieve]
29.
Conrad ME:
Sickle cell disease and hemochromatosis.
Am J Hematol
38:150,
1991[Medline]
[Order article via Infotrieve]
30.
Barton JC,
Edwards CQ,
Bertoli LF,
Shroyer TW,
Hudson SL:
Iron overload in African Americans.
Am J Med
99:616,
1995[Medline]
[Order article via Infotrieve]
31.
Wurapa RK,
Gordeuk VR,
Brittenham GM,
Khiyami A,
Schechter GP,
Edwards CQ:
Primary iron overload in African Americans.
Am J Med
101:9,
1996[Medline]
[Order article via Infotrieve]
Abstract
Introduction
Abstract
