ATP2B4 regulatory genetic variants are associated with mild malaria

BackgroundGenome-wide association studies have identified ATP2B4 as a severe malaria resistance gene. Recently, 8 potential causal regulatory variants have been shown to be associated with severe malaria.MethodsGenotyping of rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452 was performed in 154 unrelated individuals (79 controls and 75 mild malaria patients). rs10751450, rs10751451 and rs10751452 were genotyped by Taqman assays, whereas the fragment of the ATP2B4 gene containing the remaining SNPs was sequenced. Logistic regression analysis was used to assess the association between the SNPs and mild malaria.ResultsThe results showed that mild malaria was associated with rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452. The homozygous genotypes for the major alleles were associated with an increased risk of mild malaria. Furthermore, the haplotype containing the major alleles and that containing the minor alleles were the most frequent haplotypes. Individuals with the major haplotypes had a significantly higher risk of mild malaria compared to the carriers of the minor allele haplotype.ConclusionsATP2B4 polymorphisms that have been associated with severe malaria are also associated with mild malaria.

Automated summary

ATP2B4 gene, which has been identified as a severe malaria resistance gene, is also associated with mild malaria. Eight potential causal regulatory variants have been shown to be associated with severe malaria. The homozygous genotypes of these variants for the major alleles are associated with an increased risk of mild malaria.