Duffy Blood System and G6PD Genetic Variants In P. Vivax Malaria Patients From Manaus, Amazonas, Brazil

Abstract

Over a third of the world’s population lives at risk of potentially severe Plasmodium vivax induced malaria. The unique aspect of the parasite’s biology and interactions with the human host make it harder to control and eliminate the disease. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Duffy-negative blood groups are two red blood cell variations that confer protection against malaria. Molecular genotyping of G6PD and Duffy was performed in 225 patients with severe and non-severe malaria. Of the 225 patients, 29 (12.94%) and 43 (19.19%) were carriers of the G6PD c.202G>A and c.376A>G, respectively. For the Duffy genotype (c.-67T>C in the GATA promoter region), 70 (31.11%) were phenotyped as Fy(a+b-), 98 (43.55%) Fy(a+b+), 56 (24.9%) Fy(a-b+) and 1 (0.44%) Fy(a-b-). The FY*01/FY*02 genotype was prevalent in both non-severe and severe malaria. However, the frequency increased when SNP c.376A>G was also present. In women, the FY*01/FY*02 allele occurred concomitantly with c.376A>G more frequently in non-severe malaria, while in men, this combination is revealed predominantly in severe malaria. G202A and A376G G6PD variants were higher in severe malaria, with c.202G>A (RR= 4.76 – p=.009) and c.376A>G (RR: 6.47 – p<0.001) strongly associated with the trials malaria (p<0.001). Duffy phenotype Fy(a-b+) (p=0.003) and genotype FY*02/ FY*02 (p=0.007) presented the highest values parasitemia density of the vivax malaria. Research on G6PD and Duffy antigen deficiencies has been valuable, particularly when focused on densely populated areas. Altogether, c.202G>A and c.376A>G SNPs seem to be risk factors for the development of severe vivax malaria. Molecular diagnosis before treatment may be necessary in the Amazonian population and uncomplicated malaria showed a greater frequency of variation for GATA and G6PD variants than severe malaria.