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Title: CTLA4 Autoimmunity-Associated Genotype Contributes to Severe Pulmonary Tuberculosis in an African Population
Authors: Thye, T.
Scarisbrick, G.
Browne, E.N.L.
Chinbuah, M.A.
Gyapong, J.O.
Osei, I.
Owusu-Dabo, E.
Niemann, S.
Rüsch-Gerdes, S.
Meyer, C.G.
Horstmann, R.D.
Keywords: Tuberculosis
Issue Date: 2009
Publisher: PLoS ONE
Citation: PLoS ONE | July 2009 | Volume 4 | Issue 7 | e6307
Abstract: The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a singlenucleotide 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 (Pcorrected [cor] = 0.002, Pcor = 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.
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