IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB.
Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2009-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC2671601?pdf=render |
_version_ | 1818118107374288896 |
---|---|
author | Thorsten Thye Edmund N Browne Margaret A Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Norbert W Brattig Stefan Niemann Sabine Rüsch-Gerdes Rolf D Horstmann Christian G Meyer |
author_facet | Thorsten Thye Edmund N Browne Margaret A Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Norbert W Brattig Stefan Niemann Sabine Rüsch-Gerdes Rolf D Horstmann Christian G Meyer |
author_sort | Thorsten Thye |
collection | DOAJ |
description | Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions -2849 , -1082 , -819 , and -592 and reconstructed the haplotypes. The IL10 low-producer haplotype -2849A/-1082A/-819C/-592C, compared to the high-producer haplotype -2849G/-1082G/-819C/-592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3-3.6) and PPD-positive controls (OR 2.09, CI 1.2-3.5). Lower IL-10 plasma levels in homozygous -2849A/-1082A/-819C/-592C carriers, compared to homozygous -2849G/-1082G/-819C/-592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy. |
first_indexed | 2024-12-11T04:49:03Z |
format | Article |
id | doaj.art-7a48301ca91d4525b2222467107c2272 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-11T04:49:03Z |
publishDate | 2009-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-7a48301ca91d4525b2222467107c22722022-12-22T01:20:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0145e542010.1371/journal.pone.0005420IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB.Thorsten ThyeEdmund N BrowneMargaret A ChinbuahJohn GyapongIvy OseiEllis Owusu-DaboNorbert W BrattigStefan NiemannSabine Rüsch-GerdesRolf D HorstmannChristian G MeyerEvidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions -2849 , -1082 , -819 , and -592 and reconstructed the haplotypes. The IL10 low-producer haplotype -2849A/-1082A/-819C/-592C, compared to the high-producer haplotype -2849G/-1082G/-819C/-592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3-3.6) and PPD-positive controls (OR 2.09, CI 1.2-3.5). Lower IL-10 plasma levels in homozygous -2849A/-1082A/-819C/-592C carriers, compared to homozygous -2849G/-1082G/-819C/-592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy.http://europepmc.org/articles/PMC2671601?pdf=render |
spellingShingle | Thorsten Thye Edmund N Browne Margaret A Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Norbert W Brattig Stefan Niemann Sabine Rüsch-Gerdes Rolf D Horstmann Christian G Meyer IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB. PLoS ONE |
title | IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB. |
title_full | IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB. |
title_fullStr | IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB. |
title_full_unstemmed | IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB. |
title_short | IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB. |
title_sort | il10 haplotype associated with tuberculin skin test response but not with pulmonary tb |
url | http://europepmc.org/articles/PMC2671601?pdf=render |
work_keys_str_mv | AT thorstenthye il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT edmundnbrowne il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT margaretachinbuah il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT johngyapong il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT ivyosei il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT ellisowusudabo il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT norbertwbrattig il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT stefanniemann il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT sabineruschgerdes il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT rolfdhorstmann il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb AT christiangmeyer il10haplotypeassociatedwithtuberculinskintestresponsebutnotwithpulmonarytb |