Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India

Abstract

Background: Duffy blood group antigens serve as receptors for Plasmodium vivax invasion into erythrocytes, and they are determined by polymorphisms of the Duffy antigen receptor for chemokines (DARC), also known as Fy glycoprotein (FY). Duffy negativity, i.e., absence of the antigens, protects against P. vivax infection and is rare among non-African populations. However, data on DARC polymorphisms and their impact on Plasmodium infection in India are scarce.

Methods: In a case-control study among 909 malaria patients and 909 healthy community controls in Mangaluru, southwestern India, DARC polymorphisms T-33C (rs2814778), G125A (rs12075), C265T (rs34599082), and G298A (rs13962) were genotyped. Associations of the polymorphisms with the odds of malaria, parasite species and manifestation were assessed.

Results: Among patients, vivax malaria (70%) predominated over falciparum malaria (9%) and mixed species infections (21%). DARC T-33C was absent and C265T was rare (1%). FYB carriage (deduced from DARC G125A) was not associated with the risk of malaria per se but it protected against severe falciparum malaria (P = 0.03), and hospitalization (P = 0.006) due to falciparum malaria. Vice versa, carriage of DARC 298A was associated with increased odds of malaria (aOR, 1.46 (1.07-1.99), P = 0.015) and vivax malaria (aOR, 1.60 (1.14-2.22), P = 0.006) and with several reported symptoms and findings of the patients.

Conclusion: This report from southern India is the first to show an independent effect of the DARC 298A polymorphism on the risk of malaria. Functional studies are required to understand the underlying mechanism. Moreover, FYB carriage appears to protect against severe falciparum malaria in southern India.

Keywords: DARC; Duffy; India; Malaria; Plasmodium falciparum; Plasmodium vivax; SNPs.

Fig. 1

DARC 298A carriage is associated with increased odds of malaria and vivax malaria. OR, odds ratio; 95% CI, 95% confidence interval; unadjusted, crude odds ratio; adjusted, odds ratio adjusted for age, sex, and migration status; *P < 0.05 as compared to DARC G298 wildtype individuals. Forest plots display the odds of malaria according to DARC G298A genotypes. χ² test or Fisher’s exact test was applied to calculate unadjusted odds ratios (95% CIs). Adjusted odds ratios were derived from logistic regression models adjusting for age, sex and migration status. As compared to control individuals (14.5%, 132/909), DARC 298A carriage was more common in malaria patients [16.7%, 152/909; aOR, 1.46 (1.07–1.99)] and in vivax malaria patients in particular [17.7%, 112/633; aOR, 1.60 (1.14–2.22)]