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

Abstract

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.

Prevalence of α+-Thalassemia in the Scheduled Tribe and Scheduled Caste Populations of Damoh District in Madhya Pradesh, Central India

“…Moreover, this study also shows the presence of both Hb S and b-thal in the studied population. Furthermore, a + -thal is a well-known genetic factor that modulates the disease severity in sickle cell anemia and b-thal (21)(22)(23)(24)(25)(26). High prevalence of G6PD deficiency in the study area lends further support to our findings.…”

Clinical and molecular characteristics of sickle cell anemia in the northeast of Brazil

“…Sickle-cell anemia individuals with -α 2 3.7 kb thal and a CAR/Ben genotype seem to have a smaller number of painful episodes. Mukherjee et al (1997) reported a low incidence of painful crisis in individuals with -α 2 3.7 kb thalassemia and the CAR/CAR genotype, conflicting with an earlier report of Billett et al (1995) which suggest that the presence of a-thalassemia and others epistatic effects, most likely involving vascular response, should be influence the capacity of the sickle cells to adhere to the vascular endothelium. In our study, HbF levels did not show a significant difference among α-thalassemia genotypes (i.e., those with and without the α 2 3.7 kb deletion), this observation being consistent with previous reports (Figueiredo et al, 1996).…”

Genotypic influence of α-deletions on the phenotype of Indian sickle cell anemia patients

“…The genotype of α-thalassemia that is prevalent in India is α+, which is clinically silent both in the heterozygous and homozygous states. Hence, it is free from morbidity [3]. …”