Host microsatellite alleles in malaria predisposition?

Sonali Gaikwad¹ , Richa Ashma¹ , Nirbhay Kumar² , Rajni Trivedi¹ and VK Kashyap¹

¹Central Forensic Science Laboratory, National DNA Analysis Centre, 30 Gorachand Road, Kolkata-700014, West Bengal, India

²Malaria Research Institute, Department of Molecular Microbiology and Immunology, John Hopkins Bloomberg School of Public Health, E5144, 15N.Wolfe Street, Baltimore, MD 21205, USA

author email corresponding author email

Malaria Journal 2005, 4:50doi:10.1186/1475-2875-4-50


Published:	10 October 2005

Abstract

Background

Malaria is a serious, sometimes fatal, disease caused by Plasmodium infection of human red blood cells. The host-parasite co-evolutionary processes are well understood by the association of coding variations such as G6PD, Duffy blood group receptor, HLA, and beta-globin gene variants with malaria resistance. The profound genetic diversity in host is attributed to polymorphic microsatellites loci. The microsatellite alleles in bacterial species are known to have aided their survival in fatal environmental conditions. The fascinating question is whether microsatellites are genomic cushion in the human genome to combat disease stress and has cause-effect relationships with infections.

Presentation of the hypothesis

It is hypothesized that repeat units or alleles of microsatellites TH01 and D5S818, located in close proximity to beta-globin gene and immune regulatory region in human play a role in malaria predisposition. Association of alleles at aforesaid microsatellites with malaria infection was analysed. To overrule the false association in unrecognized population stratification, structure analysis and AMOVA were performed among the sampled groups.

Testing of hypothesis

Associations of microsatellite alleles with malaria infection were verified using recombination rate, Chi-square, and powerful likelihood tests. Further investigation of population genetic structure, and AMOVA was done to rule out the confounding effects of population stratification in interpretation of association studies.

Implication of the hypothesis

Lower recombination rate (θ) between microsatellites and genes implicated in host fitness; positive association between alleles -13 (D5S818), 9 (TH01) and strong susceptibility to Plasmodium falciparum; and alleles-12 (D5S818) and 6 (TH01) rendering resistance to human host were evident. The interesting fact emerging from the study was that while predisposition to malaria was a prehistoric attribute, among TH01 alleles; evolution of resistant allele-6 was a recent phenomenon, which could conceivably be driven by infection related selective forces. The host's microsatellite allelic associations with malaria infection were valid in the light of low genetic variance between sampled groups and no population stratification.