Eddie Wampande

Human genetic determinant in Mycobacterium tuberculosis complex lineage infections

Eddie M Wampande1, Sergey Nejentsev2 and Moses Joloba1

Department of immunology and Molecular Biology, College of Health Sciences Makerere University Department of medicine, Cambridge University, CB2 2QQ, UK

 Introduction:

Human-adapted Mycobacterium tuberculosis complex (MTBC) lineages are globally stratified into 7 main lineages which segregate phylo-geographically into distinct niches and this is presumed to be the basis of MTBC lineage local adaptation to specific host populations resulting from a long standing association that led to genetic exchange between the host and M.tb pathogen as a result of co-evolution.  Studies have alluded to this assertion where specific MTBC lineages are associated with particular host determinants; however such studies were done in the Caucasian populations while using a heterogeneous pool of M.tb strains and some of those studies have reported conflicting findings.

Objectives:

To characterize genes in the human genome that carry sequence variants, which are involved in M.tb diseases susceptibility.

Method:

We propose to use 200 paired samples for the host and the corresponding infecting M.tb genotype of the Ugandan population.  We shall genotype the M.tb strains using SNP assay and the human genotype by RT-PCR

Results:

The genetic associations studies between the host and pathogen shall be computed using PLINK software, to identify interacting alleles between the host and the pathogen. The association showing a P value ≤ 0.05 shall be considered significant.

 Conclusions:

The interacting alleles can be used in designing strategies for the control of Tb in future following there validation. Additionally, such data underpin the role of ethnicity in the pathogenesis of tuberculosis.