Journal article
Leprosy and the adaptation of human toll-like receptor 1.
- Abstract:
- Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 486.1KB, Terms of use)
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- Publisher copy:
- 10.1371/journal.ppat.1000979
Authors
- Publisher:
- Public Library of Science
- Journal:
- PLoS pathogens More from this journal
- Volume:
- 6
- Issue:
- 7
- Pages:
- e1000979
- Publication date:
- 2010-01-01
- DOI:
- EISSN:
-
1553-7374
- ISSN:
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1553-7366
- Language:
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English
- Keywords:
- Pubs id:
-
65274
- UUID:
-
uuid:1a3d3016-3345-4f8b-a6e3-216be9069280
- Local pid:
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pubs:65274
- Source identifiers:
-
65274
- Deposit date:
-
2012-12-19
- ARK identifier:
Terms of use
- Copyright holder:
- Wong et al
- Copyright date:
- 2010
- Notes:
- © 2010 Wong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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