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Leishmaniasis: A Genetic Link Found in Far-Flung Victims of a Lethal Form of a Parasitic Disease

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  • Leishmaniasis: A Genetic Link Found in Far-Flung Victims of a Lethal Form of a Parasitic Disease

    Leishmaniasis: A Genetic Link Found in Far-Flung Victims of a Lethal Form of a Parasitic Disease

    By DONALD G. McNEIL Jr.
    Published: January 14, 2013


    Whether someone bitten by a sandfly goes on to develop the most lethal form of leishmaniasis is determined partly by the victim?s own genes, a new study suggests.

    Leishmaniasis, caused by parasites injected by sandfly bites, has two forms: painful skin sores (known to American troops in Iraq as ?Baghdad boils?) or, in less than 20 percent of cases, the visceral form, sometimes called ?kala azar,? that attacks the organs and is fatal if untreated. About 400,000 visceral cases develop annually, 90 percent of them in three places far from one another and with different parasite subspecies: northeastern Brazil, the India-Bangladesh border and the Horn of Africa.
    ...


    Common variants in the HLA-DRB1?HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

    LeishGEN Consortium, Wellcome Trust Case Control Consortium 2, Michaela Fakiola, Amy Strange, Heather J Cordell, E Nancy Miller, Matti Pirinen, Zhan Su, Anshuman Mishra, Sanjana Mehrotra, Gloria R Monteiro, Gavin Band, C?line Bellenguez, Serge Dronov, Sarah Edkins, Colin Freeman, Eleni Giannoulatou, Emma Gray, Sarah E Hunt, Henio G Lacerda, Cordelia Langford, Richard Pearson, N?bia N Pontes, Madhukar Rai, Shri P Singh et al.

    Nature Genetics (2013) doi:10.1038/ng.2518
    Received 23 August 2012 Accepted 06 December 2012 Published online 06 January 2013

    To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1?HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed Pcombined = 2.76 ? 10−17 and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30?1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1?HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1?HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.
    ...
    Twitter: @RonanKelly13
    The views expressed are mine alone and do not represent the views of my employer or any other person or organization.
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