The fact that the average hemoglobin concentration (Hb) of AA is lower than that of whites has been documented extensively. Several investigations have shown that this difference of approximately 0.8 g/dL is due neither to iron deficiency nor to socioeconomic status. Its cause remains unknown. We compared the Hb of 1,493 AA and 31,029 white anonymized patients attending a Health Appraisal Clinic and confirmed the known difference in Hb, both for females and males (0.79 and 0.47 g/dL) respectively. The difference persisted when a subset of the subjects were paired by age and narrowed slightly in females when those with serum ferritin levels of <10 ng/ml or transferrin saturations of <16% were excluded (difference in females 0.59 g/dL; males 0.47). We determined the α-thalassemia −3.7 genotype of 298 AA. The gene frequency was found to be 0.17, and the distribution of genotypes fit the Hardy-Weinberg equilibrium. However, in a sample of 155 white subjects only one α-thalassemia allele was found (gene frequency=0.003). Among the AA subjects, the Hb and MCV values were lower in homozygotes (−a/−a) and heterozygotes (aa/−a) for α-thalassemia than in the aa/aa subjects. The table presents data for AA and white subjects after excluding all who did not have a documented serum ferritin level of >9 ng/ml and a transferrin saturation of >16%. Excluding subjects with sickle trait had no effect.

Ethnic GroupGenotypenMean HbSE HbMean MCVSE MCV
  −a/−a 11.87 0.418 72.23 2.32 
AA aa/−a 20 12.69 0.202 85.22 0.86 
  aa/aa 65 13.17 0.127 90.43 0.61 
 White  2917 13.60 0.016 90.85 0.07 
  −a/−a 13.85 0.550 83.05 1.65 
AA aa/−a 36 14.37 0.161 85.81 0.78 
  aa/aa 86 14.75 0.123 89.78 0.53 
 White  5335 15.09 0.013 90.35 0.06 
Ethnic GroupGenotypenMean HbSE HbMean MCVSE MCV
  −a/−a 11.87 0.418 72.23 2.32 
AA aa/−a 20 12.69 0.202 85.22 0.86 
  aa/aa 65 13.17 0.127 90.43 0.61 
 White  2917 13.60 0.016 90.85 0.07 
  −a/−a 13.85 0.550 83.05 1.65 
AA aa/−a 36 14.37 0.161 85.81 0.78 
  aa/aa 86 14.75 0.123 89.78 0.53 
 White  5335 15.09 0.013 90.35 0.06 

As shown in the table, the average Hb of non-iron deficient AA females and males who had 4 normal α loci (aa/aa) was 0.43 and 0.34 g/dL lower respectively than those of whites, the difference being significant with p<0.01. We conclude that one cause of the lower Hb of AA compared to white subjects is the high prevalence of α-thalassemia in the AA population, but that it accounts for only about one-quarter of the difference after iron deficiency has been excluded. There are other, as yet undefined, causes that play a role. These may include the lower ATP (

Biochem. Genet. 1:25, 1967
) and higher 2,3 BPG (
Transfusion 18:108, 1978
) levels that have been documented in the red cells of AA subjects.

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