CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population.
The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (P(corrected [cor]) = 0.002, P(cor) = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB.
Thye
Thorsten
T
Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Scarisbrick
Genevieve
G
Browne
Edmund N L
EN
Chinbuah
Margaret Amanua
MA
Gyapong
John
J
Osei
Ivy
I
Owusu-Dabo
Ellis
E
Niemann
Stefan
S
Rüsch-Gerdes
Sabine
S
Meyer
Christian G
CG
Horstmann
Rolf D
RD
D015703:Antigens, CD / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D017931:DNA Primers; D005838:Genotype; D005869:Ghana; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017931:DNA Primers