1. CTLA4 Autoimmunity-Associated Genotype Contributes to Severe Pulmonary Tuberculosis in an African Population.
- Author
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Thye, Thorsten, Scarisbrick, Genevieve, Browne, Edmund N. L., Chinbuah, Margaret Amanua, Gyapong, John, Osei, Ivy, Owusu-Dabo, Ellis, Niemann, Stefan, Rüsch-Gerdes, Sabine, Meyer, Christian G., and Horstmann, Rolf D.
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AUTOIMMUNITY ,T cells ,LYMPHOCYTES ,CD antigens ,NUCLEOTIDES ,GENETIC polymorphisms ,TUBERCULOSIS ,ETHNICITY - Abstract
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, 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. [ABSTRACT FROM AUTHOR]- Published
- 2009
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