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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number328
JournalMalaria Journal
Volume18
Issue number1
DOIs
Publication statusPublished - 24-09-2019

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Antigen Receptors
Chemokines
Malaria
India
Falciparum Malaria
Genes
Vivax Malaria
Plasmodium vivax
Blood Group Antigens
Coinfection
Case-Control Studies
Glycoproteins
Parasites
Hospitalization
Erythrocytes
Antigens
Population

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Infectious Diseases

Cite this

Gai, P. P., Van Loon, W., Siegert, K., Wedam, J., Kulkarni, S. S., Rasalkar, R., ... Mockenhaupt, F. P. (2019). Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India. Malaria Journal, 18(1), [328]. https://doi.org/10.1186/s12936-019-2966-9
Gai, Prabhanjan P. ; Van Loon, Welmoed ; Siegert, Konrad ; Wedam, Jakob ; Kulkarni, Suyamindra S. ; Rasalkar, Rashmi ; Boloor, Archith ; Kumar, Arun ; Jain, Animesh ; Mahabala, Chakrapani ; Baliga, Shantaram ; Devi, Rajeshwari ; Shenoy, Damodara ; Gai, Pramod ; Mockenhaupt, Frank P. / Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India. In: Malaria Journal. 2019 ; Vol. 18, No. 1.
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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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Gai, PP, Van Loon, W, Siegert, K, Wedam, J, Kulkarni, SS, Rasalkar, R, Boloor, A, Kumar, A, Jain, A, Mahabala, C, Baliga, S, Devi, R, Shenoy, D, Gai, P & Mockenhaupt, FP 2019, 'Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India', Malaria Journal, vol. 18, no. 1, 328. https://doi.org/10.1186/s12936-019-2966-9

Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India. / Gai, Prabhanjan P.; Van Loon, Welmoed; Siegert, Konrad; Wedam, Jakob; Kulkarni, Suyamindra S.; Rasalkar, Rashmi; Boloor, Archith; Kumar, Arun; Jain, Animesh; Mahabala, Chakrapani; Baliga, Shantaram; Devi, Rajeshwari; Shenoy, Damodara; Gai, Pramod; Mockenhaupt, Frank P.

In: Malaria Journal, Vol. 18, No. 1, 328, 24.09.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India

AU - Gai, Prabhanjan P.

AU - Van Loon, Welmoed

AU - Siegert, Konrad

AU - Wedam, Jakob

AU - Kulkarni, Suyamindra S.

AU - Rasalkar, Rashmi

AU - Boloor, Archith

AU - Kumar, Arun

AU - Jain, Animesh

AU - Mahabala, Chakrapani

AU - Baliga, Shantaram

AU - Devi, Rajeshwari

AU - Shenoy, Damodara

AU - Gai, Pramod

AU - Mockenhaupt, Frank P.

PY - 2019/9/24

Y1 - 2019/9/24

N2 - 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.

AB - 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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Gai PP, Van Loon W, Siegert K, Wedam J, Kulkarni SS, Rasalkar R et al. Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India. Malaria Journal. 2019 Sep 24;18(1). 328. https://doi.org/10.1186/s12936-019-2966-9