Skip to main content
Top
Published in: Malaria Journal 1/2019

Open Access 01-12-2019 | Falciparum Malaria | Research

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

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

Published in: Malaria Journal | Issue 1/2019

Login to get access

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.
Literature
1.
go back to reference Kwiatkowski DP. How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet. 2005;77:171–92.CrossRef Kwiatkowski DP. How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet. 2005;77:171–92.CrossRef
2.
go back to reference Driss A, Hibbert JM, Wilson NO, Iqbal SA, Adamkiewicz TV, Stiles JK. Genetic polymorphisms linked to susceptibility to malaria. Malar J. 2011;10:271.CrossRef Driss A, Hibbert JM, Wilson NO, Iqbal SA, Adamkiewicz TV, Stiles JK. Genetic polymorphisms linked to susceptibility to malaria. Malar J. 2011;10:271.CrossRef
3.
go back to reference da Silva Santos S, Clark TG, Campino S, Suarez-Mutis MC, Rockett KA, Kwiatkowski DP, et al. Investigation of host candidate malaria-associated risk/protective SNPs in a Brazilian Amazonian population. PLoS One. 2012;7:e36692.CrossRef da Silva Santos S, Clark TG, Campino S, Suarez-Mutis MC, Rockett KA, Kwiatkowski DP, et al. Investigation of host candidate malaria-associated risk/protective SNPs in a Brazilian Amazonian population. PLoS One. 2012;7:e36692.CrossRef
4.
5.
go back to reference Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, et al. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science. 1993;261:1182–4.CrossRef Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, et al. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science. 1993;261:1182–4.CrossRef
6.
go back to reference Pogo AO, Chaudhuri A. The Duffy protein: a malarial and chemokine receptor. Semin Hematol. 2000;37:122–9.CrossRef Pogo AO, Chaudhuri A. The Duffy protein: a malarial and chemokine receptor. Semin Hematol. 2000;37:122–9.CrossRef
7.
go back to reference He W, Neil S, Kulkarni H, Wright E, Agan BK, Marconi VC, et al. Duffy Antigen Receptor for Chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility. Cell Host Microbe. 2008;17(4):52–62.CrossRef He W, Neil S, Kulkarni H, Wright E, Agan BK, Marconi VC, et al. Duffy Antigen Receptor for Chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility. Cell Host Microbe. 2008;17(4):52–62.CrossRef
8.
go back to reference Horne K, Woolley IJ. Shedding light on DARC: the role of the Duffy antigen/receptor for chemokines in inflammation, infection and malignancy. Inflamm Res. 2009;58:431–5.CrossRef Horne K, Woolley IJ. Shedding light on DARC: the role of the Duffy antigen/receptor for chemokines in inflammation, infection and malignancy. Inflamm Res. 2009;58:431–5.CrossRef
9.
go back to reference Miller LH, Mason SJ, Dvorak JA, Mcginniss MH, Rothman IK. Erythrocyte receptors for (Plasmodium knowlesi) malaria: duffy blood group determinants. Science. 1975;15(189):561–3.CrossRef Miller LH, Mason SJ, Dvorak JA, Mcginniss MH, Rothman IK. Erythrocyte receptors for (Plasmodium knowlesi) malaria: duffy blood group determinants. Science. 1975;15(189):561–3.CrossRef
10.
go back to reference Howes RE, Patil AP, Piel FB, Nyangiri OA, Kabaria CW, Gething PW, et al. The global distribution of the Duffy blood group. Nat Commun. 2011;2:266.CrossRef Howes RE, Patil AP, Piel FB, Nyangiri OA, Kabaria CW, Gething PW, et al. The global distribution of the Duffy blood group. Nat Commun. 2011;2:266.CrossRef
11.
go back to reference Albuquerque SRL, De Oliveira Cavalcante F, Sanguino EC, Tezza L, Castilho F, Lilian C, et al. FY polymorphisms and vivax malaria in inhabitants of Amazonas State, Brazil. Parasitol Res. 2010;106:1049–53.CrossRef Albuquerque SRL, De Oliveira Cavalcante F, Sanguino EC, Tezza L, Castilho F, Lilian C, et al. FY polymorphisms and vivax malaria in inhabitants of Amazonas State, Brazil. Parasitol Res. 2010;106:1049–53.CrossRef
12.
go back to reference Iwamoto S, Li J, Sugimoto N, Okuda H, Kajii E. Characterization of the Duffy gene promotor: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals. Biochem Biophys Res Commun. 1996;222:852–9.CrossRef Iwamoto S, Li J, Sugimoto N, Okuda H, Kajii E. Characterization of the Duffy gene promotor: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals. Biochem Biophys Res Commun. 1996;222:852–9.CrossRef
13.
go back to reference McMorran BJ, Wieczorski L, Drysdale KE, Chan JA, Huang HM, Smith C, et al. Platelet factor 4 and duffy antigen required for platelet killing of Plasmodium falciparum. Science. 2012;338:1348–51.CrossRef McMorran BJ, Wieczorski L, Drysdale KE, Chan JA, Huang HM, Smith C, et al. Platelet factor 4 and duffy antigen required for platelet killing of Plasmodium falciparum. Science. 2012;338:1348–51.CrossRef
14.
go back to reference McMorran BJ, Burgio G, Foote SJ. New insights into the protective power of platelets in malaria infection. Commun Integr Biol. 2013;6:e23653.CrossRef McMorran BJ, Burgio G, Foote SJ. New insights into the protective power of platelets in malaria infection. Commun Integr Biol. 2013;6:e23653.CrossRef
15.
go back to reference King CL, Adams JH, Xianli J, Grimberg BT, McHenry AM, Greenberg LJ, et al. Fya/Fyb antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria. Proc Natl Acad Sci USA. 2011;108:20113–8.CrossRef King CL, Adams JH, Xianli J, Grimberg BT, McHenry AM, Greenberg LJ, et al. Fya/Fyb antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria. Proc Natl Acad Sci USA. 2011;108:20113–8.CrossRef
16.
go back to reference Chittoria A, Mohanty S, Jaiswal YK, Das A. Natural selection mediated association of the Duffy (FY) gene polymorphisms with Plasmodium vivax malaria in India. PLoS One. 2012;7:e45219.CrossRef Chittoria A, Mohanty S, Jaiswal YK, Das A. Natural selection mediated association of the Duffy (FY) gene polymorphisms with Plasmodium vivax malaria in India. PLoS One. 2012;7:e45219.CrossRef
17.
go back to reference Kar S, Seth S, Seth PK. Duffy blood groups and malaria in the ao nagas in Nagaland, India. Hum Hered. 1991;41:231–5.CrossRef Kar S, Seth S, Seth PK. Duffy blood groups and malaria in the ao nagas in Nagaland, India. Hum Hered. 1991;41:231–5.CrossRef
18.
go back to reference Singh IP, Walter H, Bhasin MK, Bhardwaj V, Sudhakar K. Genetic markers and malaria. Observations in Gujarat, India. Hum Hered. 1986;36:31–6.CrossRef Singh IP, Walter H, Bhasin MK, Bhardwaj V, Sudhakar K. Genetic markers and malaria. Observations in Gujarat, India. Hum Hered. 1986;36:31–6.CrossRef
19.
go back to reference Verma IC, Thakur A. Duffy blood group determinants and malaria in India. J Genet. 1993;72:15–9.CrossRef Verma IC, Thakur A. Duffy blood group determinants and malaria in India. J Genet. 1993;72:15–9.CrossRef
20.
go back to reference WHO. World malaria report. Geneva: World Health Organization; 2018. WHO. World malaria report. Geneva: World Health Organization; 2018.
21.
go back to reference Malaguarnera L, Musumeci S. The immune response to Plasmodium falciparum malaria. Lancet Infect Dis. 2002;2:472–8.CrossRef Malaguarnera L, Musumeci S. The immune response to Plasmodium falciparum malaria. Lancet Infect Dis. 2002;2:472–8.CrossRef
22.
go back to reference Gai PP, Mockenhaupt FP, Siegert K, Wedam J, Boloor A, Kulkarni SS, et al. Manifestation of malaria in Mangaluru, southern India. Malar J. 2018;17:313.CrossRef Gai PP, Mockenhaupt FP, Siegert K, Wedam J, Boloor A, Kulkarni SS, et al. Manifestation of malaria in Mangaluru, southern India. Malar J. 2018;17:313.CrossRef
23.
go back to reference Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol. 1993;58:283–92.CrossRef Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol. 1993;58:283–92.CrossRef
24.
go back to reference Makroo RN, Bhatia A, Gupta R, Phillip J. Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population. Indian J Med Res. 2013;137:521–6.PubMedPubMedCentral Makroo RN, Bhatia A, Gupta R, Phillip J. Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population. Indian J Med Res. 2013;137:521–6.PubMedPubMedCentral
25.
go back to reference Miller LH, Mason SJ, Clyde DF, McGinniss MH. The resistance factor to Plasmodium vivax in blacks. N Engl J Med. 1976;295:302–4.CrossRef Miller LH, Mason SJ, Clyde DF, McGinniss MH. The resistance factor to Plasmodium vivax in blacks. N Engl J Med. 1976;295:302–4.CrossRef
26.
go back to reference Yazdanbakhsh K, Rios M, Storry JR, Kosower N, Parasol N, Chaudhuri A, et al. Molecular mechanisms that lead to reduced expression of Duffy antigens. Transfusion. 2000;40:310–20.CrossRef Yazdanbakhsh K, Rios M, Storry JR, Kosower N, Parasol N, Chaudhuri A, et al. Molecular mechanisms that lead to reduced expression of Duffy antigens. Transfusion. 2000;40:310–20.CrossRef
27.
go back to reference Lentsch AB. The Duffy antigen/receptor for chemokines (DARC) and prostate cancer. A role as clear as black and white? FASEB J. 2002;16:1093–5.CrossRef Lentsch AB. The Duffy antigen/receptor for chemokines (DARC) and prostate cancer. A role as clear as black and white? FASEB J. 2002;16:1093–5.CrossRef
28.
go back to reference Aitken EH, Alemu A, Rogerson SJ. Neutrophils and malaria. Front Immunol. 2018;9:3005.CrossRef Aitken EH, Alemu A, Rogerson SJ. Neutrophils and malaria. Front Immunol. 2018;9:3005.CrossRef
29.
go back to reference de Leoratti FMS, Trevelin SC, Cunha FQ, Rocha BC, Costa PAC, Gravina HD, et al. Neutrophil paralysis in Plasmodium vivax malaria. PLoS Negl Trop Dis. 2012;6:e1710.CrossRef de Leoratti FMS, Trevelin SC, Cunha FQ, Rocha BC, Costa PAC, Gravina HD, et al. Neutrophil paralysis in Plasmodium vivax malaria. PLoS Negl Trop Dis. 2012;6:e1710.CrossRef
30.
go back to reference Singh K, Mukherjee P, Shakri AR, Singh A, Pandey G, Bakshi M, et al. Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial. NPJ Vaccines. 2018;3:48.CrossRef Singh K, Mukherjee P, Shakri AR, Singh A, Pandey G, Bakshi M, et al. Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial. NPJ Vaccines. 2018;3:48.CrossRef
Metadata
Title
Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India
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
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2019
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-019-2966-9

Other articles of this Issue 1/2019

Malaria Journal 1/2019 Go to the issue