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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Leprosy and the adaptation of human toll-like receptor 1
PLoS Pathogens, Volume 6, No. 7, Article e1000979, Year 2010
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Description
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 = 5.7×10-8, OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9×10-14, 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. © 2010 Wong et al.
Available Materials
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https://efashare.b-cdn.net/share/pmc/articles/PMC2895660/bin/ppat.1000979.s009.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2895660/bin/ppat.1000979.s010.doc
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https://efashare.b-cdn.net/share/pmc/articles/PMC2895660/bin/ppat.1000979.s021.doc
Authors & Co-Authors
Wong, Sunny H.
Unknown Affiliation
Gochhait, Sailesh
Unknown Affiliation
Malhotra, Dheeraj K.
Unknown Affiliation
Pettersson, Fredrik H.
Unknown Affiliation
Teo, Yik Ying
Unknown Affiliation
Khor, Chiea Chuen
Unknown Affiliation
Rautanen, Anna
Unknown Affiliation
Chapman, Stephen James
Unknown Affiliation
Mills, Tara C.
Unknown Affiliation
Srivastava, Amit
Unknown Affiliation
Rudko, Aleksey
Unknown Affiliation
Freidin, Maxim B.
Unknown Affiliation
Puzyrev, Valery Pavlovich
Unknown Affiliation
Ali, Shafat
Unknown Affiliation
Aggarwal, Shweta
Unknown Affiliation
Chopra, Rupali
Unknown Affiliation
Reddy, Belum S.N.
Unknown Affiliation
Garg, Vijay K.
Unknown Affiliation
Roy, Suchismita
Unknown Affiliation
Meisner, Sarah J.
Unknown Affiliation
Hazra, Sunil K.
Unknown Affiliation
Saha, Bibhuti
Unknown Affiliation
Floyd, Sian
Unknown Affiliation
Keating, Brendan J.
Unknown Affiliation
Kim, Cecilia
Unknown Affiliation
Fairfax, Benjamin Peter
Unknown Affiliation
Knight, Julian C.
Unknown Affiliation
Hill, Philip C.
Unknown Affiliation
Adegbola, Richard A.
Unknown Affiliation
Håkonarson, Håkon H.
Unknown Affiliation
Fine, Paul E.M.
Unknown Affiliation
Pitchappan, Ramasamy M.
Unknown Affiliation
Bamezai, Rameshwar N.K.
Unknown Affiliation
Hill, Adrian V. S.
Unknown Affiliation
Vannberg, Fredrik O.
Unknown Affiliation
Statistics
Citations: 146
Authors: 35
Affiliations: 13
Identifiers
Doi:
10.1371/journal.ppat.1000979
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study
Case-Control Study