1Departement of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 2Medstar Health Research Institute, Hyattsville, MD, 3GOCADAN Department, Norton Sound Health Corporation, Nome, AK, 4Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC
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Individuals and populations differ in regard to susceptibility or resistance to infectious disease. Here we examine whether genetic factors contribute to variation in antibody titer, which represents history of infection with a particular pathogen, in Alaskan Eskimos (primarily Inupiat). Participants included ~500 family members from the Norton Sound region of Alaska, who take part in the Genetics of Coronary Artery Disease in Alaskan Natives (GOCADAN) study. Antibody titers and seroprevalence were determined at two time points, approximately 15 years apart. IgG antibody levels were determined using ELISA for: Helicobacter pylori (Hp), cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1) and -2 (HSV-2); and IgG, IgA, and IgM antibodies to Chlamydophila pneumoniae (Cp) were quantified by microimmunofluorescence. Additive genetic heritability (h2) was calculated using variance component (VC) pedigree analysis with the computer program SOLAR. Genome-wide linkage analysis was performed using 383 STRs. Seroprevalence rates indicate that infection with these pathogens is common (>75% for Hp, CMV, and HSV-1) and chronic (seroreversion rates are <1% to 10% over ~15 years). Heritability estimates are significant for four pathogens, with h2 ranging from 0.33 to 0.61 (for Hp and Cp, respectively). Results for HSV-2, the only sexually transmitted pathogen examined, are not significant. Significant genome-wide linkage results were obtained for Cp, with a maximum LOD score of 4.84 on chromosome 8. These results demonstrate that individual genetic differences influence antibody measures of common infections in this population. Further investigation may identify specific genetic factors that contribute to infection susceptibility and elucidate the underlying immunological processes involved.
This study was funded in part by NIH, HL064244