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

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-alpha 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, Pless than or equal to0.001). 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.