Distribution of the Duffy genotypes in Malaysian Borneo and its relation to Plasmodium knowlesi malaria susceptibility

Autoři: Jeremy Ryan de Silva aff001;  Amirah Amir aff001;  Yee Ling Lau aff001;  Choo-Huck Ooi aff002;  Mun Yik Fong aff001
Působiště autorů: Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia aff001;  Sarawak State Health Department, Jalan Diplomatik, Off Jalan Bako, Kuching, Sarawak, Malaysia aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222681


The Duffy blood group plays a key role in Plasmodium knowlesi and Plasmodium vivax invasion into human erythrocytes. The geographical distribution of the Duffy alleles differs between regions with the FY*A allele having high frequencies in many Asian populations, the FY*B allele is found predominately in European populations and the FY*Bes allele found predominantly in African regions. A previous study in Peninsular Malaysia indicated high homogeneity of the dominant FY*A/FY*A genotype. However, the distribution of the Duffy genotypes in Malaysian Borneo is currently unknown. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Malaysian Borneo were determined. A total of 79 P. knowlesi patient blood samples and 76 healthy donor samples were genotyped using allele specific polymerase chain reaction (ASP-PCR). Subsequently a P. knowlesi invasion assay was carried out on FY*AB/ FY*A and FY*A/ FY*A Duffy genotype blood to investigate if either genotype conferred increased susceptibility to P. knowlesi invasion. Our results show almost equal distribution between the homozygous FY*A/FY*A and heterozygous FY*A/FY*B genotypes. This is in stark contrast to the Duffy distribution in Peninsular Malaysia and the surrounding Southeast Asian region which is dominantly FY*A/FY*A. The mean percent invasion of FY*A/FY*A and FY*A/FY*B blood was not significantly different indicating that neither blood group confers increased susceptibility to P. knowlesi invasion.

Klíčová slova:

Biology and life sciences – Biogeography – Evolutionary biology – Genetics – Population genetics – Phylogeography – Heredity – Genetic mapping – Variant genotypes – Population biology – Cell biology – Cellular types – Animal cells – Blood cells – Red blood cells – Anatomy – Body fluids – Blood – Blood groups – Physiology – Parasitology – Parasite groups – Apicomplexa – Plasmodium – Molecular biology – Molecular biology techniques – Artificial gene amplification and extension – Polymerase chain reaction – Ecology and environmental sciences – Earth sciences – Geography – People and places – Geographical locations – Asia – Borneo – Malaysia – Medicine and health sciences – Research and analysis methods


1. Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet. 2004;363(9414):1017–24. Epub 2004/03/31. doi: 10.1016/S0140-6736(04)15836-4 15051281.

2. Moyes CL, Henry AJ, Golding N, Huang Z, Singh B, Baird JK, et al. Defining the geographical range of the Plasmodium knowlesi reservoir. PLoS Negl Trop Dis. 2014;8(3):e2780. Epub 2014/03/29. doi: 10.1371/journal.pntd.0002780 24676231.

3. Jongwutiwes S, Putaporntip C, Iwasaki T, Sata T, Kanbara H. Naturally acquired Plasmodium knowlesi malaria in human, Thailand. Emerg Infect Dis. 2004;10(12):2211–3. Epub 2005/01/25. doi: 10.3201/eid1012.040293 15663864.

4. Ng OT, Ooi EE, Lee CC, Lee PJ, Ng LC, Pei SW, et al. Naturally acquired human Plasmodium knowlesi infection, Singapore. Emerg Infect Dis. 2008;14(5):814–6. Epub 2008/04/29. doi: 10.3201/eid1405.070863 18439370.

5. Zhu HM, Li J, Zheng H. [Human natural infection of Plasmodium knowlesi]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2006;24(1):70–1. Epub 2006/07/27. 16866152.

6. Malaysia Ministry of Health. Zoonotic Malaria And The Prevention Program In Malaysia. 2018. http://www.moh.gov.my/index.php/database_stores/store_view_page/21/1087.

7. Cutbush M, Mollison PL. The Duffy blood group system. Heredity (Edinb). 1950;4(3):383–9. Epub 1950/12/01. doi: 10.1038/hdy.1950.31 14802995.

8. Ikin EW, Mourant AE, Pettenkofer HJ, Blumenthal G. Discovery of the expected haemagglutinin, anti-Fyb. Nature. 1951;168(4288):1077–8. Epub 1951/12/22. doi: 10.1038/1681077b0 14910641.

9. Mathew S, Chaudhuri A, Murty VV, Pogo AO. Confirmation of Duffy blood group antigen locus (FY) at 1q22—>q23 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;67(1):68. Epub 1994/01/01. doi: 10.1159/000133801 8187556.

10. Chaudhuri A, Polyakova J, Zbrzezna V, Pogo AO. The coding sequence of Duffy blood group gene in humans and simians: restriction fragment length polymorphism, antibody and malarial parasite specificities, and expression in nonerythroid tissues in Duffy-negative individuals. Blood. 1995;85(3):615–21. Epub 1995/02/01. 7833466.

11. Iwamoto S, Li J, Sugimoto N, Okuda H, Kajii E. Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals. Biochem Biophys Res Commun. 1996;222(3):852–9. Epub 1996/05/24. doi: 10.1006/bbrc.1996.0833 8651934.

12. 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. Epub 2011/04/07. doi: 10.1038/ncomms1265 21468018.

13. Lee JS, Frevert CW, Wurfel MM, Peiper SC, Wong VA, Ballman KK, et al. Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J Immunol. 2003;170(10):5244–51. Epub 2003/05/08. doi: 10.4049/jimmunol.170.10.5244 12734373.

14. Anstee DJ. The relationship between blood groups and disease. Blood. 2010;115(23):4635–43. Epub 2010/03/24. doi: 10.1182/blood-2010-01-261859 20308598.

15. Reich D, Nalls MA, Kao WH, Akylbekova EL, Tandon A, Patterson N, et al. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet. 2009;5(1):e1000360. Epub 2009/01/31. doi: 10.1371/journal.pgen.1000360 19180233.

16. Miller LH, Mason SJ, Clyde DF, McGinniss MH. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med. 1976;295(6):302–4. Epub 1976/08/05. doi: 10.1056/NEJM197608052950602 778616.

17. Miller LH, Mason SJ, Dvorak JA, McGinniss MH, Rothman IK. Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants. Science. 1975;189(4202):561–3. Epub 1975/08/15. doi: 10.1126/science.1145213 1145213.

18. Barnwell JW, Nichols ME, Rubinstein P. In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax. J Exp Med. 1989;169(5):1795–802. Epub 1989/05/01. doi: 10.1084/jem.169.5.1795 2469769.

19. De Silva JR, Lau YL, Fong MY. Genotyping of the Duffy blood group among Plasmodium knowlesi-infected patients in Malaysia. PLoS One. 2014;9(9):e108951. Epub 2014/10/01. doi: 10.1371/journal.pone.0108951 25268233.

20. Barber BE, William T, Grigg MJ, Menon J, Auburn S, Marfurt J, et al. A prospective comparative study of knowlesi, falciparum, and vivax malaria in Sabah, Malaysia: high proportion with severe disease from Plasmodium knowlesi and Plasmodium vivax but no mortality with early referral and artesunate therapy. Clin Infect Dis. 2013;56(3):383–97. Epub 2012/10/23. doi: 10.1093/cid/cis902 23087389.

21. William T, Menon J, Rajahram G, Chan L, Ma G, Donaldson S, et al. Severe Plasmodium knowlesi malaria in a tertiary care hospital, Sabah, Malaysia. Emerg Infect Dis. 2011;17(7):1248–55. Epub 2011/07/19. doi: 10.3201/eid1707.101017 21762579.

22. Singh B, Daneshvar C. Plasmodium knowlesi malaria in Malaysia. Med J Malaysia. 2010;65(3):166–72. Epub 2011/09/24. 21939162.

23. Imwong M, Tanomsing N, Pukrittayakamee S, Day NP, White NJ, Snounou G. Spurious amplification of a Plasmodium vivax small-subunit RNA gene by use of primers currently used to detect P. knowlesi. J Clin Microbiol. 2009;47(12):4173–5. Epub 2009/10/09. doi: 10.1128/JCM.00811-09 19812279.

24. Amir A, Russell B, Liew JW, Moon RW, Fong MY, Vythilingam I, et al. Invasion characteristics of a Plasmodium knowlesi line newly isolated from a human. Sci Rep. 2016;6:24623. Epub 2016/04/22. doi: 10.1038/srep24623 27097521.

25. Hamblin MT, Di Rienzo A. Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. Am J Hum Genet. 2000;66(5):1669–79. Epub 2000/04/14. doi: 10.1086/302879 10762551.

26. Hamblin MT, Thompson EE, Di Rienzo A. Complex signatures of natural selection at the Duffy blood group locus. Am J Hum Genet. 2002;70(2):369–83. Epub 2001/12/26. doi: 10.1086/338628 11753822.

27. Noizat-Pirenne F. Relevance of blood groups in transfusion of sickle cell disease patients. C R Biol. 2013;336(3):152–8. Epub 2013/05/07. doi: 10.1016/j.crvi.2012.09.011 23643398.

28. Babinszki A, Berkowitz RL. Haemolytic disease of the newborn caused by anti-c, anti-E and anti-Fya antibodies: report of five cases. Prenat Diagn. 1999;19(6):533–6. Epub 1999/07/23. doi: 10.1002/(sici)1097-0223(199906)19:6<533::aid-pd570>3.0.co;2-5 10416968.

29. Nathalang O, Intharanut K, Siriphanthong K, Nathalang S, Kupatawintu P. Duffy blood group genotyping in Thai blood donors. Ann Lab Med. 2015;35(6):618–23. Epub 2015/09/12. doi: 10.3343/alm.2015.35.6.618 26354350.

30. Nathalang O, Kuvanont S, Punyaprasiddhi P, Tasaniyanonda C, Sriphaisal T. A preliminary study of the distribution of blood group systems in Thai blood donors determined by the gel test. Southeast Asian J Trop Med Public Health. 2001;32(1):204–7. Epub 2001/08/04. 11485086.

31. Shimizu Y, Ao H, Soemantri A, Tiwawech D, Settheetham-Ishida W, Kayame OW, et al. Sero- and molecular typing of Duffy blood group in Southeast Asians and Oceanians. Hum Biol. 2000;72(3):511–8. Epub 2000/07/08. 10885196.

32. Peng CT, Tsai CH, Lee HH, Lin CL, Wang NM, Chang JG. Molecular analysis of Duffy, Yt and Colton blood groups in Taiwanese, Filipinos and Thais. Kaohsiung J Med Sci. 2000;16(2):63–7. Epub 2000/05/19. 10816988.

33. Liu Z, Zeng R, Chen Q, Li M, Shi GY, Wei P, et al. Genotyping for Kidd, Kell, Duffy, Scianna, and RHCE blood group antigens polymorphisms in Jiangsu Chinese Han. Chin Med J (Engl). 2012;125(6):1076–81. Epub 2012/05/23. 22613534.

34. Zhou S, Liu M, An W, Liang X, Yu W, Piao F. A New Method for Analyzing the Duffy Blood Group Genotype by TaqMan Minor Groove Binding Probes. J Clin Lab Anal. 2015;29(3):203–7. Epub 2014/05/07. doi: 10.1002/jcla.21751 24798509.

35. King CL, Adams JH, Xianli J, Grimberg BT, McHenry AM, Greenberg LJ, et al. Fy(a)/Fy(b) antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria. Proc Natl Acad Sci U S A. 2011;108(50):20113–8. Epub 2011/11/30. doi: 10.1073/pnas.1109621108 22123959.

36. Martins ML, da Silva AR, Santos HC, Alves MT, Schmidt LC, Vertchenko SB, et al. Duffy blood group system: New genotyping method and distribution in a Brazilian extra-Amazonian population. Mol Cell Probes. 2017;35:20–6. Epub 2017/06/08. doi: 10.1016/j.mcp.2017.06.001 28587995.

37. Mason SJ, Miller LH, Shiroishi T, Dvorak JA, McGinniss MH. The Duffy blood group determinants: their role in the susceptibility of human and animal erythrocytes to Plasmodium knowlesi malaria. Br J Haematol. 1977;36(3):327–35. Epub 1977/07/01. 70210. doi: 10.1111/j.1365-2141.1977.tb00656.x 70210

38. Lim KL, Amir A, Lau YL, Fong MY. The Duffy binding protein (PkDBPalphaII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes. Malar J. 2017;16(1):331. Epub 2017/08/13. doi: 10.1186/s12936-017-1984-8 28800732.

39. Fong MY, Cheong FW, Lau YL. Erythrocyte-binding assays reveal higher binding of Plasmodium knowlesi Duffy binding protein to human Fy(a+/b+) erythrocytes than to Fy(a+/b-) erythrocytes. Parasit Vectors. 2018;11(1):527. Epub 2018/09/28. doi: 10.1186/s13071-018-3118-8 30257710.

40. Miri-Moghaddam E, Bameri Z, Mohamadi M. Duffy blood group genotypes among malaria Plasmodium vivax patients of Baoulch population in Southeastern Iran. Asian Pac J Trop Med. 2014;7(3):206–7. Epub 2014/02/11. doi: 10.1016/S1995-7645(14)60021-3 24507640.

41. Monhaty SS, S K, Fotedar R, Lakshminarayana J, Parihar R. Prevalance of Duffy blood groups among the population of the desert region of India. J Rural Trop Pub Health. 2011;10:53–6.

42. Cavasini CE, de Mattos LC, Couto AA, Couto VS, Gollino Y, Moretti LJ, et al. Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region. Malar J. 2007;6:167. Epub 2007/12/21. doi: 10.1186/1475-2875-6-167 18093292.

Článek vyšel v časopise


2019 Číslo 9