title: Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris.
abstract: Inherited chromosomally integrated human herpesvirus-6 (iciHHV-6) results in the germ-line transmission of the HHV-6 genome. Every somatic cell of iciHHV-6+ individuals contains the HHV-6 genome integrated in the telomere of chromosomes. Whether having iciHHV-6 predisposes humans to diseases remains undefined. DNA from 19,597 participants between 40 and 69 years of age were analyzed by quantitative PCR (qPCR) for the presence of iciHHV-6. Telomere lengths were determined by qPCR. Medical records, hematological, biochemical, and anthropometric measurements and telomere lengths were compared between iciHHV-6+ and iciHHV-6- subjects. The prevalence of iciHHV-6 was 0.58%. Two-way ANOVA with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on continuous outcomes. Two-way logistic regression with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on disease prevalence. Of 50 diseases monitored, a single one, angina pectoris, is significantly elevated (3.3×) in iciHHV-6+ individuals relative to iciHHV-6- subjects (P = 0.017; 95% CI, 1.73-6.35). When adjusted for potential confounding factors (age, body mass index, percent body fat, and systolic blood pressure), the prevalence of angina remained three times greater in iciHHV-6+ subjects (P = 0.015; 95%CI, 1.23-7.15). Analyses of telomere lengths between iciHHV-6- without angina, iciHHV-6- with angina, and iciHHV-6+ with angina indicate that iciHHV-6+ with angina have shorter telomeres than age-matched iciHHV-6- subjects (P = 0.006). Our study represents, to our knowledge, the first large-scale analysis of disease association with iciHHV-6. Our results are consistent with iciHHV-6 representing a risk factor for the development of angina.
authors.affiliation: Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC, Canada G1V 4G2;
authors.forename: Annie
authors.initials: A
authors.lastname: Gravel
authors.affiliation: Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC, Canada G1V 4G2;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dubuc
authors.affiliation: Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC, Canada G1V 4G2;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Morissette
authors.affiliation: Molecular Virology Laboratory, Department of Laboratory Medicine, University of Washington, Seattle, WA 98102;
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Sedlak
authors.affiliation: Molecular Virology Laboratory, Department of Laboratory Medicine, University of Washington, Seattle, WA 98102; Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98102;
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC, Canada G1V 4G2; Department of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, Université Laval, Quebec City, QC, Canada G1V 0A6 louis.flamand@crchul.ulaval.ca.
authors.forename: Louis
authors.initials: L
authors.lastname: Flamand
mesh_terms: D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000235:genetics / Q000821:virology*; D005260:Female; D020022:Genetic Predisposition to Disease; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016615:Telomere
keywords: HHV-6; angina; chromosomal integration; ciHHV-6; telomere