Abstract
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 −33rd and the 125th 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.
Highlights
The human Duffy blood-group (Fy) antigens are major determinants for the invasion of malaria parasite Plasmodium vivax in RBCs and are encoded by Duffy (FY) gene which is characterized by three different alleles at the genetic level; FY*A, FY*B and FY*O [1–3]
Since ecoclimatic factors are highly variable in India with complex malaria epidemiology due to both P. vivax and P. falciparum infections [11] and Indians are genetically heterogeneous with complex population history [12,13,14]; we were interested to determine (i) the variable distribution of FY gene polymorphisms and genetic differentiations among populations living in different eco-climatic conditions, and
In order to catch most of the polymorphisms of the FY gene and to meaningfully conduct population genetic survey, we have divided the whole of India into six distinct zones; viz., North India (NI), Central India (CI), West India (WI), South India (SI), East India (EI) and North-East India (NEI)
Summary
The human Duffy blood-group (Fy) antigens are major determinants for the invasion of malaria parasite Plasmodium vivax in RBCs and are encoded by Duffy (FY) gene which is characterized by three different alleles at the genetic level; FY*A, FY*B and FY*O [1–3]. In none of the 250 Indians, the C nucleotide at the 233rd promoter region of the FY gene could be found (no FY*O allele), indicating no Duffy-negative individual in the presently analyzed samples from India.
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