Both heterozygous and homozygous α+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Abstract

Although the ␣ ؉ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous ␣ ؉ thalassemia was reduced in both case patients with severe malaria (ad-

Selection and Mutation for α Thalassemia in Nonmalarial and Malarial Environments

“…Another study in Ghana (Mockenhaupt et al, 2004) also found a large effect with a standardized OR value for α + thalassemia heterozygotes of 0.577. However, they did not observe an effect in homozygotes, a finding that Williams et al (2005a) suggested was due to low statistical power.…”

“…Recently, the deletional mutation rate for α globin (Lam & Jeffreys, 2006) and the amount of protection for α thalassemia genotypes in malarial environments have been estimated (Allen et al, 1997;Williams et al, 2005a). Here I use these values to examine the expected pattern of selection in nonmalarial environments and the dynamics of selection in malarial environments for α globin deletion variants.…”

“…Two studies have shown protection from severe malaria for heterozygous and homozygous individuals with α + thalassemia, compared to individuals without α + thalassemia (Allen et al, 1997;Williams et al, 2005a). Using the data from the large case-control study in Kenya (Williams et al, 2005a) and the formula above, the OR values of α + heterozygotes and homozygotes standardized to the normal αα/αα genotype are 0.623 and 0.522 for severe malaria, respectively (Table 2).…”

“…Two studies have shown protection from severe malaria for heterozygous and homozygous individuals with α + thalassemia, compared to individuals without α + thalassemia (Allen et al, 1997;Williams et al, 2005a). Using the data from the large case-control study in Kenya (Williams et al, 2005a) and the formula above, the OR values of α + heterozygotes and homozygotes standardized to the normal αα/αα genotype are 0.623 and 0.522 for severe malaria, respectively (Table 2). In the other case-control study in Papua New Guinea (Allen et al, 1997), the OR values of α + thalassemia heterozygotes and homozygotes, standardized to the normal αα/αα genotype, are 0.781 and 0.362 for severe malaria, respectively, a smaller effect for −α/αα heterozygotes and a larger effect for −α/−α homozygotes than in the Kenyan study.…”

“…Two large-scale studies using the case-control approach (Allen et al, 1997;Williams et al, 2005a) in populations with high frequencies of α + thalassemia have estimated the odds ratios (OR) for α + thalassemia heterozygotes and homozygotes. Below I will estimate the selection coefficients for these genotypes from these data.…”