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Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection

Genes & Immunity volume 8, pages 539–551 (2007)Cite this article

Abstract

Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3–q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH−; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analyzed for association with DTH+/− status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P=0.005; 95% CI=1.28–3.97) and TGFBI (OR 1.94; P=0.003; 95% CI=1.24–3.03). VL child/parent trios gave no evidence of association, but the DTH− phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P=0.006; 95% CI=1.38–7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P=0.042; 95% CI=1.04–8.65). These results indicate several genes in the immune response gene cluster at 5q23.3–q31.1 influence outcomes of L. chagasi infection in this region of Brazil.

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Acknowledgements

This research was supported by National Institutes of Health grants AI048822 (MEW), AI45540 (MEW), NIH TMRC grant AI30639 (SMBJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (SMBJ), Merit Review and Gulf War grants from the Department of Veterans’ Affairs (MEW), The Wellcome Trust (JMB and HJC) and in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.

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  1. J M Blackwell and M E Wilson: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil

    S M B Jeronimo, D R A Martins, F L Bezerra, E T Nascimento, G R Monteiro & H G Lacerda

  2. Departments of Internal Medicine, Microbiology, Epidemiology and the Molecular Biology Program, University of Iowa and the VA Medical Center, Iowa City, IA, USA

    A K B Holst, N A Ettinger & M E Wilson

  3. Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, UK

    S E Jamieson, R Francis, E N Miller & J M Blackwell

  4. Institute of Human Genetics, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne, UK

    H J Cordell

  5. Inherited Disease Research Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA

    P Duggal

  6. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    T H Beaty

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Electronic database information

1) http://www.who.int/tdr/diseases/leish/diseaseinfo.htm

2)www.appliedbiosystems.com

3) http://www.stata.com/

4) http://www-gene.cimr.cam.ac.uk/clayton/software/stata/

5) http://www.hapmap.org/

6) http://www-gene.cimr.cam.ac.uk/clayton/software/

7) http://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi?dirDB=TF_8.3

8) http://www.bioinformatik.de/cgi-bin/browse/Catalog/Software/Prediction_of_Prediction_of_Transcription_Factor_Binding_Sites/

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Jeronimo, S., Holst, A., Jamieson, S. et al. Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection. Genes Immun 8, 539–551 (2007). https://doi.org/10.1038/sj.gene.6364422

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