title: 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-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, P< or =0.001). 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.
authors.affiliation: Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. JWL8@CDC.GOV
authors.forename: J
authors.initials: J
authors.lastname: Lingappa
authors.forename: T
authors.initials: T
authors.lastname: Kuffner
authors.forename: J
authors.initials: J
authors.lastname: Tappero
authors.forename: W
authors.initials: W
authors.lastname: Whitworth
authors.forename: A
authors.initials: A
authors.lastname: Mize
authors.forename: R
authors.initials: R
authors.lastname: Kaiser
authors.forename: J
authors.initials: J
authors.lastname: McNicholl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D004196:Disease Outbreaks; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000378:metabolism; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D007919:Leptospira / Q000302:isolation & purification*; D007922:Leptospirosis / Q000453:epidemiology* / Q000235:genetics* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014871:Water Microbiology; D014881:Water Supply
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C063831:HLA-DQ6 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha; D004247:DNA