The Role of α-Thalassemia and Iron Deficiency in the Difference between Hemoglobin Levels of African-Americans (AA) and Whites.

Abstract

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/−a311.870.41872.232.32FAAaa/−a2012.690.20285.220.86aa/aa6513.170.12790.430.61White291713.600.01690.850.07−a/−a213.850.55083.051.65MAAaa/−a3614.370.16185.810.78aa/aa8614.750.12389.780.53White533515.090.01390.350.06As 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.