An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population
Human 5q23-32 contains a cluster of genes (IL3/4/5/9) for interleukins commonly associated with disease exacerbatory T helper 2 immune responses in mycobacterial infections. Human 17q11.2-q12 contains the gene (NOS2A) encoding macrophage-expressed inducible nitric oxide synthase (iNOS), which genera...
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ndltd-bl.uk-oai-ethos.bl.uk-5966772015-03-20T06:00:48ZAn immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian populationBlack, G. F.1997Human 5q23-32 contains a cluster of genes (IL3/4/5/9) for interleukins commonly associated with disease exacerbatory T helper 2 immune responses in mycobacterial infections. Human 17q11.2-q12 contains the gene (NOS2A) encoding macrophage-expressed inducible nitric oxide synthase (iNOS), which generates toxic nitric oxide for antimicrobial activity, and an array of genes (SCYA1/2/5) encoding small inducible chemokines which act as monocyte chemoattractants and are involved in inflammatory responses. To study the role of these two regions in human disease susceptibility, DNA from a series of 40 multicase leprosy (220 individuals) and 48 multicase TB (402 individuals) families were genotyped for microsatellite, variable number tandem repeat, or restriction fragment length polymorphisms within or adjacent to the candidate gene regions. In addition to clinical disease phenotypes, results of immunological assays (T cell proliferation and interferon-γ cytokine responses to mycobacterial antigens) were used to ascertain responder/nonresponder phenotypes for genetic analysis. A sub-set of families were also examined to ascertain whether polymorphism at the IL-4 locus influenced IL-4 production in response to non-specific stimulation. The results of this work show that in this Brazilian population genes in the region of 17q11.2-q12 may have some influence over the control of susceptibility to TB. Although there is no evidence that genes in the 5q23-q32 region are involved in susceptibility to TB or leprosy per se, results indicate that this region may play a role in controlling both T-cell proliferative and IFN-γ production responses to antigenic stimulation. Results also demonstrate a possible association between a homozygous IL-4 genotype and low IL-4 production.616.042University of Cambridgehttp://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596677Electronic Thesis or Dissertation |
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616.042 Black, G. F. An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population |
description |
Human 5q23-32 contains a cluster of genes (IL3/4/5/9) for interleukins commonly associated with disease exacerbatory T helper 2 immune responses in mycobacterial infections. Human 17q11.2-q12 contains the gene (NOS2A) encoding macrophage-expressed inducible nitric oxide synthase (iNOS), which generates toxic nitric oxide for antimicrobial activity, and an array of genes (SCYA1/2/5) encoding small inducible chemokines which act as monocyte chemoattractants and are involved in inflammatory responses. To study the role of these two regions in human disease susceptibility, DNA from a series of 40 multicase leprosy (220 individuals) and 48 multicase TB (402 individuals) families were genotyped for microsatellite, variable number tandem repeat, or restriction fragment length polymorphisms within or adjacent to the candidate gene regions. In addition to clinical disease phenotypes, results of immunological assays (T cell proliferation and interferon-γ cytokine responses to mycobacterial antigens) were used to ascertain responder/nonresponder phenotypes for genetic analysis. A sub-set of families were also examined to ascertain whether polymorphism at the IL-4 locus influenced IL-4 production in response to non-specific stimulation. The results of this work show that in this Brazilian population genes in the region of 17q11.2-q12 may have some influence over the control of susceptibility to TB. Although there is no evidence that genes in the 5q23-q32 region are involved in susceptibility to TB or leprosy per se, results indicate that this region may play a role in controlling both T-cell proliferative and IFN-γ production responses to antigenic stimulation. Results also demonstrate a possible association between a homozygous IL-4 genotype and low IL-4 production. |
author |
Black, G. F. |
author_facet |
Black, G. F. |
author_sort |
Black, G. F. |
title |
An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population |
title_short |
An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population |
title_full |
An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population |
title_fullStr |
An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population |
title_full_unstemmed |
An immunogenetic study of susceptibility to leprosy and tuberculosis in a Brazilian population |
title_sort |
immunogenetic study of susceptibility to leprosy and tuberculosis in a brazilian population |
publisher |
University of Cambridge |
publishDate |
1997 |
url |
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596677 |
work_keys_str_mv |
AT blackgf animmunogeneticstudyofsusceptibilitytoleprosyandtuberculosisinabrazilianpopulation AT blackgf immunogeneticstudyofsusceptibilitytoleprosyandtuberculosisinabrazilianpopulation |
_version_ |
1716794873141526528 |