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 act...

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Bibliographic Details
Published in:PloS one 2009-07, Vol.4 (7), p.e6307-e6307
Main Authors: 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, Horstmann, Rolf D
Format: Article
Language:English
Subjects:
Alleles
Antigens
Antigens, CD - immunology
Autoimmune diseases
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Autoimmunity
Base Sequence
Case-Control Studies
Community
CTLA-4 Antigen
CTLA-4 protein
Cytokines
Cytotoxicity
DNA Primers
Gene frequency
Genes
Genetic aspects
Genetics and Genomics/Genetics of Disease
Genotype
Ghana
Haplotypes
Health services
Hepatitis
Human immunodeficiency virus
Humans
Infections
Infectious Diseases/Respiratory Infections
Lymphocytes
Lymphocytes T
Medical research
Medicine
Minority & ethnic groups
Mycobacterium
Pathogens
Phosphorylation
Polymorphism
Polymorphism, Single Nucleotide
Pulmonary tuberculosis
Radiographs
Radiography
Radiology and Medical Imaging
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Smear
T cells
Thyroid diseases
Tuberculosis
Tuberculosis, Pulmonary - genetics
Tuberculosis, Pulmonary - immunology
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0006307