Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis.
Melioidosis is a tropical infection caused by the Gram-negative soil saprophyte Burkholderia pseudomallei. Despite broad exposure of northeastern Thais, disease develops in only a small proportion of individuals. Although diabetes is a risk factor, the mechanisms of host susceptibility to melioidosi...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1797095625053962240 |
|---|---|
| author | West, T Chierakul, W Chantratita, N Limmathurotsakul, D Wuthiekanun, V Emond, M Hawn, T Peacock, S Skerrett, S |
| author_facet | West, T Chierakul, W Chantratita, N Limmathurotsakul, D Wuthiekanun, V Emond, M Hawn, T Peacock, S Skerrett, S |
| author_sort | West, T |
| collection | OXFORD |
| description | Melioidosis is a tropical infection caused by the Gram-negative soil saprophyte Burkholderia pseudomallei. Despite broad exposure of northeastern Thais, disease develops in only a small proportion of individuals. Although diabetes is a risk factor, the mechanisms of host susceptibility to melioidosis are still poorly understood. We postulated that Toll-like receptors (TLRs) regulate host susceptibility to disease, and that genetic variation in TLRs is associated with melioidosis. We analyzed the frequency of eight previously described TLR pathway polymorphisms in 490 cases compared with 950 non-hospitalized controls or 458 hospitalized controls. Based on these results, we then analyzed the frequency of additional TLR4 or TLR6-1-10 region polymorphisms in cases and controls. We found that the TLR4(1196C>T) variant was associated with protection from melioidosis when compared with non-hospitalized controls. The TLR1(742A>G) and TLR1(-7202A>G) variants were associated with melioidosis when compared with hospitalized controls. In further analyses, we found that two additional TLR4 region polymorphisms were associated with disease. In diabetics, three other TLR6-1-10 region polymorphisms were associated with disease when compared with hospitalized controls. We conclude that TLR genetic variants may modulate host susceptibility to melioidosis. Confirmation of these findings and further investigation of the mechanisms are required. |
| first_indexed | 2024-03-07T04:30:33Z |
| format | Journal article |
| id | oxford-uuid:ce25b482-2a47-49ac-88c2-b47be9ebbec8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:30:33Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:ce25b482-2a47-49ac-88c2-b47be9ebbec82022-03-27T07:33:45ZToll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ce25b482-2a47-49ac-88c2-b47be9ebbec8EnglishSymplectic Elements at Oxford2012West, TChierakul, WChantratita, NLimmathurotsakul, DWuthiekanun, VEmond, MHawn, TPeacock, SSkerrett, SMelioidosis is a tropical infection caused by the Gram-negative soil saprophyte Burkholderia pseudomallei. Despite broad exposure of northeastern Thais, disease develops in only a small proportion of individuals. Although diabetes is a risk factor, the mechanisms of host susceptibility to melioidosis are still poorly understood. We postulated that Toll-like receptors (TLRs) regulate host susceptibility to disease, and that genetic variation in TLRs is associated with melioidosis. We analyzed the frequency of eight previously described TLR pathway polymorphisms in 490 cases compared with 950 non-hospitalized controls or 458 hospitalized controls. Based on these results, we then analyzed the frequency of additional TLR4 or TLR6-1-10 region polymorphisms in cases and controls. We found that the TLR4(1196C>T) variant was associated with protection from melioidosis when compared with non-hospitalized controls. The TLR1(742A>G) and TLR1(-7202A>G) variants were associated with melioidosis when compared with hospitalized controls. In further analyses, we found that two additional TLR4 region polymorphisms were associated with disease. In diabetics, three other TLR6-1-10 region polymorphisms were associated with disease when compared with hospitalized controls. We conclude that TLR genetic variants may modulate host susceptibility to melioidosis. Confirmation of these findings and further investigation of the mechanisms are required. |
| spellingShingle | West, T Chierakul, W Chantratita, N Limmathurotsakul, D Wuthiekanun, V Emond, M Hawn, T Peacock, S Skerrett, S Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. |
| title | Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. |
| title_full | Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. |
| title_fullStr | Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. |
| title_full_unstemmed | Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. |
| title_short | Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. |
| title_sort | toll like receptor 4 region genetic variants are associated with susceptibility to melioidosis |
| work_keys_str_mv | AT westt tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT chierakulw tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT chantratitan tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT limmathurotsakuld tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT wuthiekanunv tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT emondm tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT hawnt tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT peacocks tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis AT skerretts tolllikereceptor4regiongeneticvariantsareassociatedwithsusceptibilitytomelioidosis |