Nepalese populations show no association between the distribution of malaria and protective alleles

Abstract

Malaria is perhaps the most important parasitic infection and strongest known force for selection in the recent evolutionary history of the human genome. Genetically-determined resistance to malaria has been well-documented in some populations, mainly from Africa. The disease is also endemic in South Asia, the world's second most populous region, where resistance to malaria has also been observed, for example in Nepal. The biological basis of this resistance, however, remains unclear. We have therefore investigated whether known African resistance alleles also confer resistance in Asia. We typed seven single nucleotide polymorphisms (SNPs) from the genes HBB, FY, G6PD, TNFSF5, TNF, NOS2 and FCGR2A in 928 healthy individuals from Nepal. Five loci were found to be fixed for the non-resistant allele (HBB, FY, G6PD, TNFSF5 and NOS2). The remaining two (rs1800629 and rs1801274) showed the presence of the resistant allele at a frequency of 93% and 27% in TNF and FCGR2A, respectively. However, the frequencies of these alleles did not differ significantly between highland (susceptible) and lowland (resistant) populations. The observed differences in allele and genotype frequencies in Nepalese populations therefore seem to reflect demographic processes or other selective forces in the Himalayan region, rather than malaria selection pressure actin on these alleles.

Figure 1

Distribution of malaria-protective alleles (black sectors) in Nepal. Red lines indicate populations from malaria-endemic lowland regions, black lines from malaria-free highland regions. A) rs1800629 (TNF), B) rs1801274 (FCGRIIA).