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, protec...

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Bibliographic Details
Published in:Malaria Journal
Main Authors: Prabhanjan P. Gai, Welmoed van Loon, Konrad Siegert, Jakob Wedam, Suyamindra S. Kulkarni, Rashmi Rasalkar, Archith Boloor, Arun Kumar, Animesh Jain, Chakrapani Mahabala, Shantaram Baliga, Rajeshwari Devi, Damodara Shenoy, Pramod Gai, Frank P. Mockenhaupt
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2019
Subjects:
Duffy
DARC
SNPs
Malaria
India
Plasmodium vivax
Arctic medicine. Tropical medicine
RC955-962
Infectious and parasitic diseases
RC109-216
Arctic
Online Access:https://doi.org/10.1186/s12936-019-2966-9
https://doaj.org/article/29112fda7761419bb6078ce5d1f0cecd
Description
Summary: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.

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