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Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes

Genes & Immunity volume 2, pages 196–204 (2001)Cite this article

Abstract

Previous analyses indicate major gene control of susceptibility to leprosy per se and the HLA class II region has been implicated in determining susceptibility and control of clinical phenotype. Segregation analysis using data from 76 Brazilian leprosy multi-case pedigrees (1166 individuals) supported a two locus model as the best fit: a recessive major gene and a recessive modifier gene(s) (single locus vs two locus model, P = 0.0007). Combined segregation and linkage analysis to the major locus, showed strong linkage to HLA class II (HLA-DQB1 P = 0.000002, HLA-DQA1 P = 0.000002, HLA-DRB1 P = 0.0000003) and tumour necrosis factor genes (TNF P = 0.00002, LTA P = 0.003). Extended transmission disequilibrium testing, using multiple affected family members, demonstrated that the common allele TNF*1 of the −308 promoter region polymorphism showed linkage and/or association with disease per se, at a high level of significance (P < 0.0001). Two locus transmission disequilibrium testing suggested susceptibility (TNF*1/LTA*2) and protective (TNF*2/LTA*2) haplotypes in the class iii region. Taken together the segregation and HLA analyses suggest the possibility of more than one susceptibility locus in the MHC.

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Acknowledgements

We would like to thank the people of Belém for their contribution to this study.

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Author notes

  1. JJ Shaw

    Present address: Department of Parasitology, Sao Paulo University, Institute of Biomedical Sciences, 05508–900, SP, Brazil

Authors and Affiliations

  1. Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2XY, UK

    M-A Shaw, CS Peacock & JM Blackwell

  2. University of Leeds, School of Biology, Miall Building, Clarendon Way, Leeds, LS2 9JT, UK

    M-A Shaw & IJ Donaldson

  3. Genetic Epidemiology, Duthie Building (808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

    A Collins

  4. Instituto Evandro Chagas, Caixa Postal 3, 66.001, Belém, Pará, Brazil

    Z Lins-Lainson, JJ Shaw, F Ramos & F Silveira

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  1. M-A Shaw
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Correspondence to M-A Shaw.

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This study was funded by a Wellcome Trust grant to JMB.

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Shaw, MA., Donaldson, I., Collins, A. et al. Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes . Genes Immun 2, 196–204 (2001). https://doi.org/10.1038/sj.gene.6363754

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