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. 1991 Feb;48(2):390–397.

Protection against malaria morbidity: Near-fixation of the α-thalassemia gene in a Nepalese population

G Modiano, G Morpurgo, L Terrenato, A Novelletto, A Di Rienzo, B Colombo, M Purpura, M Mariani, S Santachiara-Benerecetti, A Brega, K A Dixit, S L Shrestha, A Lania, W Wanachiwanawin, L Luzzatto
PMCID: PMC1683029  PMID: 1990845

Abstract

We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of β-thal, βs, G6PD (−), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of α-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous α-/α-genotype and an overall α-thal gene (α-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with α-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the α-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.

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Selected References

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