EFFECT OF ALPHA-THALASSEMIA ON SICKLE-CELL-ANEMIA LINKED TO THE ARAB-INDIAN HAPLOTYPE IN INDIA

Two population groups from Western India with a high prevalence of the beta(S) gene, one tribal (Valsad) and the other nontribal (Nagpur), w ere studied. The beta(S) gene frequency in both populations was simila r (0.22 vs. 0.23), but not the clinical expression of sickle-cell anem ia (SS): the sickle homozygotes in the tribal group appeared to have a mild clinical course, whereas the majority in the nontribal group exh ibited a more severe clinical phenotype, Both tribal and nontribal SS patients had a similarly high mean hemoglobin (Hb)F expression (18.5% vs. 15.5%) and a high number of F cells (72.3% vs, 66.6%). DNA analysi s of the beta-globin gene cluster region revealed that in these two po pulations, this portion of DNA was identical with and corresponded to the typical Arab-Indian haplotype. Nevertheless, in heterozygotes, the mean beta(S) expression was lower (27.9%) in the tribal as compared t o the nontribal group (35.5%). The major epistatic factor distinguishi ng the milder presentation in tribals vs. a more severe manifestation in nontribals was the very high frequency (0.97) of the alpha-thalasse mia gene in the former as compared to the latter (0.24). We conclude t hat the phenotypic expression of sickle-cell anemia, linked to the Ara b-India haplotype and expressing similar levels of HbF and F cells, is not uniformly mild in India and that alpha-thalassemia is a powerful and additional epistatic factor in the Indian subcontinent. (C) 1997 W iley-Liss, Inc.