The concurrence of malaria and hemoglobinopathies, observed in malaria endemic regions, reflects the phenomenon of natural selection. Since the life cycle of the malaria parasite has an erythrocytic stage, abnormalities in the red blood cells (RBCs) hinder the parasite's survival in the human host. Hemoglobin (Hb) variants affect the life span of RBCs and thus lower the chance of infection by the parasite. While a change in just one of the Hb genes offers some protection against malaria, change in both alleles results in β-thalassemia major (β-TM). A striking geographical heterogeneity of β-thalassemia (β-thal) has been observed. Moving from Mexico in the west to China towards the east, the spectrum of mutations in the β-globin gene has been seen to vary. In the western end of the thalassemia belt, defects in the first intervening sequence (IVS-I) and exon 2 of the β-globin gene are more common, while on the eastern coast, IVS-II and exon 1 are also vulnerable to mutations. The worldwide increase in the incidence of β-TM mandates the need for efficient measures to reduce β-thal births, and the geographical heterogeneity of β-thal alleles reduces the burden of genetic testing of fetuses suspected of carrying a mutant allele. In the present review, the common mutations in the global thalassemia belt have been illustrated, and the possible factors that affect the mutagenicity of sites have been discussed. A biogeographic analysis that may provide insight into the non biological factors influencing different loci in the β-globin gene in different geographical regions is suggested.
In the present study, iron toxicity, as indicated by DNA damage, has been seen to vary in the patients. Thus, monitoring of the dose of iron chelators, according to the type of mutation in the beta globin gene, may help improve the compliance of beta thalassemics to chelation therapy and prevent side-effects in patients with beta plus mutations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.