Journal article

Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry

Lesley-Ann Gray, Heather A D'Antoine, Steven YC Tong, Melita McKinnon, Dawn Bessarab, Ngiare Brown, Bo Remenyi, Andrew Steer, Genevieve Syn, Jenefer M Blackwell, Michael Inouye, Jonathan R Carapetis

JOURNAL OF INFECTIOUS DISEASES | OXFORD UNIV PRESS INC | Published : 2017

Abstract

Background: Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells. Methods: Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single-nucleotide polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. Results: The strongest genetic association was intronic to ..

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