Associations between human leukocyte antigen class I variants and the Mycobacterium tuberculosis subtypes causing disease.
BACKGROUND
The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process.


METHODS
Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping.


RESULTS
We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen.


CONCLUSIONS
This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.
MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg.
Muneeb
M
Salie
Lize
L
van der Merwe
Marlo
M
Möller
Michelle
M
Daya
Gian D
GD
van der Spuy
Paul D
PD
van Helden
Maureen P
MP
Martin
Xiao-Jiang
XJ
Gao
Robin M
RM
Warren
Mary
M
Carrington
Eileen G
EG
Hoal
D000328:Adult; D000483:Alleles; D004251:DNA Transposable Elements; D005260:Female; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology*; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D013019:South Africa; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology*; D055815:Young Adult
D004251:DNA Transposable Elements; D015395:Histocompatibility Antigens Class I
Mycobacterium tuberculosis; coadaptation; host–pathogen; human leukocyte antigens; susceptibility; tuberculosis