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HLA-DQ6 and ingestion of contaminated water: possible gene–environment interaction in an outbreak of Leptospirosis

Abstract

Leptospirosis is a zoonosis that can cause severe multisystem disease. While host gene-environment interactions likely modify infectious disease susceptibility, including for leptopsirosis, this has not been documented. In a 1998 leptospirosis outbreak investigation among triathletes in a lake swim, swallowing lake-water was a disease risk-factor. We used genomic DNA from 85 anonymized blood-sample remainders from that investigation to examine the association of laboratory-confirmed leptospirosis with gene polymorphisms (TNF-α alleles and serologically defined genotypes for HLA-DRB1 and HLA-DQB1). HLA-DQ6-positive triathletes had increased risk of laboratory-confirmed leptospirosis (OR=2.8, P=0.04) compared to DQ6-negatives. DQ6-positive triathletes swallowing lake-water had greatest risk (OR 8.46, P0.001). This first report of a genetic risk-factor affecting susceptibility to leptospirosis is also the first documented gene–environment interaction (DQ6 and swallowed water) affecting infectious disease susceptibility. Based on these preliminary findings, we hypothesize a role for superantigens in leptospirosis and underscore the importance of outbreak investigations for understanding infectious disease gene–environment interactions.

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Acknowledgements

We thank Juliette Morgan, Mary Bajani-Ari and Sandra Bragg for access to the outbreak investigation epidemiologic and diagnostic data. Muin Khoury, David A Ashford, Nancy Rosenstein, Bradley Perkins and Catherine Staunton provided critical comments on the manuscript; Brian Plikaytis, Tom Taylor and Mike Hoekstra were invaluable advisors for the statistical analysis.

Funding for this study was obtained through the CDC National Center for Infectious Diseases' Genetics Working Group.

Conflict of Interest: There were no conflicts of interest associated with work reported in this manuscript for any of the authors involved in this study.

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Correspondence to J Lingappa.

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Supplementary Information accompanies the paper on Genes and Immunity's website (http://www.nature.com/gene

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Lingappa, J., Kuffner, T., Tappero, J. et al. HLA-DQ6 and ingestion of contaminated water: possible gene–environment interaction in an outbreak of Leptospirosis. Genes Immun 5, 197–202 (2004). https://doi.org/10.1038/sj.gene.6364058

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