African Americans at risk for increased iron stores or liver disease.

PURPOSE: We sought to determine the prevalence of elevated measures of iron status in African Americans and whether the combination of serum ferritin concentration >200 microg/L for women or >300 microg/L for men and transferrin saturation in the highest quartile represents increased likelihood of mutation of HFE, self-reported iron overload or self-reported liver disease. SUBJECTS AND METHODS: A cross-sectional observational study of 27,224 African Americans > or =25 years of age recruited in a primary care setting was conducted as part of the multi-center, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study. Measurements included serum ferritin concentration, transferrin saturation, testing for HFE C282Y and H63D, and self-reported iron overload and liver disease. RESULTS: Serum ferritin concentration >200 microg/L for women or >300 microg/L for men occurred in 5263 (19.3%) of African Americans, while serum ferritin concentration in this range with highest-quartile transferrin saturation (>29% women; >35% men) occurred in 1837 (6.7%). Adjusted odds of HFE mutation (1.76 women, 1.67 men), self-reported iron overload (1.97 women, 2.88 men), or self-reported liver disease (5.18 women, 3.73 men) were greater with elevated serum ferritin concentration and highest-quartile transferrin saturation than with nonelevated serum ferritin concentration (each P <.05). CONCLUSIONS: Serum ferritin concentration >200 microg/L for women or >300 microg/L for men in combination with transferrin saturation >29% for women or >35% for men occurs in approximately 7% of adult African American primary care patients. Patients with this combination of iron test results should be evaluated for increased body iron stores or liver disease.

Human leukocyte antigen haplotypes and HFE mutations in Spanish hereditary hemochromatosis and sporadic porphyria cutanea tarda.

BACKGROUND AND AIMS: It has been postulated that the HFE C282Y mutation (linked to human leukocyte antigen [HLA]-A3-B7 haplotype) is not only responsible for hereditary hemochromatosis; HLA class I alleles would also contribute to the disease pathogenesis. In addition, H63D mutation linked to HLA-A29-B44 would also be pathogenetic, particularly in the Mediterranean Basin and throughout the world. However, sporadic porphyria cutanea tarda (s-PCT) has also been linked to these HFE mutations. In the present work, we have studied HFE mutations and HLA genes to test these hypotheses. METHODS: C282Y and H63D mutations together with HLA genetic typing have been performed in Spanish hereditary hemochromatosis (n = 98) and PCT (n = 63) patients. The etiologic fraction (delta) has been used to determine the absolute strongest gene linkage to both diseases. RESULTS: The Spanish frequent HLA-A29-B44 haplotype is not significantly associated to the H63D mutations in hereditary hemochromatosis patients (although it is found more frequently in patients than in controls). Sporadic porphyria cutanea tarda patients do not show a significant association to H63D mutations, although it is also more frequent than in controls; however, compound H63D/C282Y subjects seem to bear a significant risk to s-PCT. Allelic C282Y (and not H63D) frequencies show a significant association with s-PCT. CONCLUSIONS: The postulated additional risk of hereditary hemochromatosis given by class I HLA antigens may be secondary to the HFE gene linkage disequilibrium with certain class I alleles or to the existence of other neighboring genetic pathogenetic factors in our Spanish sample.

Associations of iron overload in Africa with hepatocellular carcinoma and tuberculosis: Strachan's 1929 thesis revisited.

We analyzed data from the first study of iron overload in Africans, conducted between 1925 and 1928, to determine whether this common condition is associated with death from hepatocellular carcinoma and/or tuberculosis. In the original study, necropsies were performed on 714 adult blacks from southern Africa. Hepatic and splenic iron levels were measured semiquantitatively in 604 subjects and one of five iron grades was assigned. We examined death from hepatocellular carcinoma or from tuberculosis and the variables of age, sex, the presence of cirrhosis or other diagnoses that might be influenced by iron status, and tissue iron grades. Nineteen percent of men and 16% of women had the highest grade of hepatic iron. After adjustment for the presence of cirrhosis, hepatic iron grade was the variable most significantly associated with death from hepatocellular carcinoma (P = .021). The odds of death from hepatocellular carcinoma in subjects with the highest grade of hepatic iron was 23.5 (95% confidence interval, 2.1 to 225) times the odds in subjects with the three lowest grades. Splenic iron was the variable most significantly associated with death from tuberculosis (P <.0001). The odds of death from tuberculosis with the highest grade of splenic iron was 16.9 (4.8 to 59.9) times the odds with the two lowest grades. These findings suggest that iron overload in black Africans may be a risk factor for death from hepatocellular carcinoma and for death from tuberculosis.