期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：26
页码：8058-8063
DOI：10.1073/pnas.1502741112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceBased on several studies, including ours, we estimate that 40-70 million individuals carry a chromosomally integrated copy of the human herpesvirus 6 (HHV-6) genome in every cell of their body. This condition is referred to as inherited chromosomally integrated HHV-6 (iciHHV-6). The regions targeted for integration are telomeres, which play important roles in the self-renewal capacity of cells. Whether iciHHV-6 is associated with disease remains unknown. After conducting a population screen (n = 20,000), our results indicate that the prevalence of angina is three times greater in iciHHV-6+ subjects relative to iciHHV-6- ones. Furthermore, iciHHV-6+ subjects have shorter telomeres, a result that may explain, at least in part, how iciHHV-6 may contribute to the development of angina. 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 (3.3x) 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.
