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The Duffy (Fy) antigens act as receptors for chemokines as well as for  Plasmodium vivax  to invade human RBCs. A recent study has correlated the occurrence of the  FY*A  allele of Duffy gene with decreased susceptibility to vivax malaria, but no epidemiological correlation between the distribution of FY *A  allele and incidences of vivax malaria has been established so far. Furthermore, if such correlations exist, whether natural selection has mediated the association, is an important question. Since India is highly endemic to  P. vivax  malaria with variable eco-climatic and varying vivax malaria epidemiology across different regions, such a question could well be answered in Indians. For this, we have genotyped the  FY  gene at the −33 rd  and the 125 th  nucleotide positions in 250 Indians sampled from six different zonal plus one tribal population covering the whole of India and studied possible correlations with eco-climatic and vivax malaria incidences. No  FY*O  allele was found, however, both the  FY*A  and  FY*B  alleles forming  FY*A/FY*A ,  FY*A/FY*B  and  FY*B/FY*B  genotypes were widely distributed among Indians. Five out of seven population samples significantly deviated from the Hardy-Weinberg equilibrium expectation, and two alleles  (FY*A  and  FY*B ) and the homozygote genotype,  FY*B / FY*B  were clinally distributed over the population coordinates. Furthermore, vivax malaria incidences over the past five years were significantly negatively and positively associated with the frequencies of the  FY*A  and  FY*B  alleles, respectively. The Northern Indians were highly differentiated from the other zonal population samples at the  FY  gene, as evidenced from the reconstructed Neighbor-Joining phylogenetic tree. The results specify the role of natural selection in the distribution of  FY  gene polymorphism in India. Furthermore, the hypotheses on the part of the  FY*A  allele in conferring protection to vivax malaria could be validated following population genetic studies in a vivax malaria epidemiological setting, such as India.

Natural Selection Mediated Association of the Duffy (FY) Gene Polymorphisms with Plasmodium vivax Malaria in India