title: CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population.
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, 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.
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Thye
authors.forename: Genevieve
authors.initials: G
authors.lastname: Scarisbrick
authors.forename: Edmund N L
authors.initials: EN
authors.lastname: Browne
authors.forename: Margaret Amanua
authors.initials: MA
authors.lastname: Chinbuah
authors.forename: John
authors.initials: J
authors.lastname: Gyapong
authors.forename: Ivy
authors.initials: I
authors.lastname: Osei
authors.forename: Ellis
authors.initials: E
authors.lastname: Owusu-Dabo
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.forename: Sabine
authors.initials: S
authors.lastname: Rüsch-Gerdes
authors.forename: Christian G
authors.initials: CG
authors.lastname: Meyer
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Horstmann
mesh_terms: 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*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017931:DNA Primers