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 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.
Thye
Thorsten
T
Bernhard Nocht Institute for Tropical Medicine, Department of Molecular Medicine, Hamburg, Germany. thye@bni-hamburg.de
Browne
Edmund N
EN
Chinbuah
Margaret A
MA
Gyapong
John
J
Osei
Ivy
I
Owusu-Dabo
Ellis
E
Brattig
Norbert W
NW
Niemann
Stefan
S
Rüsch-Gerdes
Sabine
S
Horstmann
Rolf D
RD
Meyer
Christian G
CG
D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005869:Ghana; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D011401:Promoter Regions, Genetic; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology* / Q000635:transmission
D017931:DNA Primers; C508609:IL10 protein, human; D016753:Interleukin-10