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Indian Journal of Human Genetics
Medknow Publications on behalf of Indian Society of Human Genetics
ISSN: 0971-6866 EISSN: 1998-362x
Vol. 14, Num. 2, 2008, pp. 70-70

Indian Journal of Human Genetics, Vol. 14, No. 2, May-August, 2008, pp. 70

Letter to the Editor

Falciparum malaria selected while HIV-1 slaughtered

Ghosh Kanjaksha, Shetty Shrimati, Mota Leenam

Department of Haemostasis, National Institute of Immunohaematology (ICMR), 13th Floor, KEM Hospital, Parel, Mumbai
Correspondence Address:Institute of Immunohaematology (ICMR), 13th Floor, KEM Hospital, Parel, Mumbai
kanjakshaghosh@yahoo.com

Code Number: hg08016

Sir,

Human leukocyte antigen (HLA) is one of the most polymorphic systems known to man and its direct involvement in immune response is well known. It is generally accepted that two major infections, i.e. falciparum malaria and tuberculosis, exerted extreme selective pressure to fashion our genome as we see it today. Of the two, falciparum malaria is more important in tropical and sub tropical areas where the disease has been endemic for centuries.

The development of HLA polymorphism and resistance to malaria make interesting reading. [1],[2] In different populations, different HLA polymorphisms were linked to resistance to malaria. However HLA B35 came up as one of the alleles in several population groups where falciparum malaria is endemic. [3],[4] In India, HLA B35 is a common allele with 12-36% frequency among various populations and caste groups exposed for centuries to falciparum malaria. A study also has shown that HLA B35 can present HIV1 Gag protein (aa20-50 RPGGKKRYMIKHLVWASRELERFALNPGL) to generate cytotoxic T lymphocytes. [5] Simultaneously several studies from all over the world have shown that HLA B35 is associated with faster disease progression in HIV1 infection. [6]

Falciparum malaria, by way of positive selection, has given human beings an Achilles heel in the form of HLA B35 through which the HIV arrow is now passing. The study of HLA in human population gives us an unusual insight i.e. malaria selected HLA B35 positive population, only for it to be slaughtered by HIV1 infection in future. Nature is blind and unforgiving in driving evolution!

References

1.Hill AV, Elvin J, Willis AC, Aidoo M, Allsopp CE, Gotch FM, et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 1992;360:434-9.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Hill AV. Malaria resistance genes: A natural selection. Trans R Soc Trop Med Hyg 1992;86:225-32.  Back to cited text no. 2  [PUBMED]  
3.Shankarkumar U, Devaraj JP, Ghosh K, Karnad D, Anand K, Mohanty D. HLA associations in P. falciparum malaria patients from Mumbai, western India. Indian J Malariol 2002;39:76-82.  Back to cited text no. 3    
4.Contu L, Carcassi C, Orru S, Mulargia M, Arras M, Boero R, et al. HLA-B35 frequency variations correlate with malaria infection in Sardinia. Tissue Antigens 1998;52:452-61.  Back to cited text no. 4    
5.Thakar MR, Bhonge LS, Lakhashe SK, Shankarkumar U, Sane SS, Kulkarni SS, et al. Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and Nef.J Infect Dis 2005;192:749-59.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, et al. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N Engl J Med 2001;344:1668-75.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]

Copyright 2008 - Indian Journal of Human Genetics

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