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There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions.

Original publication

DOI

10.1375/1369052042663887

Type

Journal article

Journal

Twin Res

Publication Date

12/2004

Volume

7

Pages

578 - 588

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Antigens, Antigens, CD, Antigens, Differentiation, CTLA-4 Antigen, Cell Proliferation, Cytokines, Gambia, Genotype, Humans, Interleukin-10, Middle Aged, Mycobacterium tuberculosis, Polymorphism, Genetic, Receptors, Interleukin-4, Rural Population, T-Lymphocytes, Twins