Effect of α-thalassemia on sickle-cell anemia linked to the Arab-Indian haplotype in India

✍ Scribed by Mukherjee, Malay B.; Lu, Chang Yong; Ducrocq, Rolande; Gangakhedkar, Raman R.; Colah, Roshan B.; Kadam, Megha D.; Mohanty, Dipika; Nagel, Ronald L.; Krishnamoorthy, Rajagopal

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 138 KB
• Volume: 55
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199706)55:2<104::aid-ajh9>3.0.co;2-x

✦ Synopsis

Two population groups from Western India with a high prevalence of the ␤ S gene, one tribal (Valsad) and the other nontribal (Nagpur), were studied. The ␤ S gene frequency in both populations was similar (0.22 vs. 0.23), but not the clinical expression of sickle-cell anemia (SS): the sickle homozygotes in the tribal group appeared to have a mild clinical course, whereas the majority in the nontribal group exhibited 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 analysis of the ␤-globin gene cluster region revealed that in these two populations, this portion of DNA was identical with and corresponded to the typical Arab-Indian haplotype. Nevertheless, in heterozygotes, the mean ␤ S expression was lower (27.9%) in the tribal as compared to the nontribal group (35.5%). The major epistatic factor distinguishing the milder presentation in tribals vs. a more severe manifestation in nontribals was the very high frequency (0.97) of the ␣-thalassemia gene in the former as compared to the latter (0.24). We conclude that the phenotypic expression of sickle-cell anemia, linked to the Arab-India haplotype and expressing similar levels of HbF and F cells, is not uniformly mild in India and that ␣-thalassemia is a powerful and additional epistatic factor in the Indian subcontinent. Am.