Gravel Annie, Dubuc Isabelle, Morissette Guillaume, Sedlak Ruth H, Jerome Keith R, Flamand Louis
Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec City, QC, Canada G1V 4G2;
Molecular Virology Laboratory, Department of Laboratory Medicine, University of Washington, Seattle, WA 98102;
Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):8058-63. doi: 10.1073/pnas.1502741112. Epub 2015 Jun 15.
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.
遗传性染色体整合人疱疹病毒6型（iciHHV - 6）导致HHV - 6基因组的种系传播。iciHHV - 6阳性个体的每个体细胞都含有整合在染色体端粒中的HHV - 6基因组。携带iciHHV - 6是否会使人类易患疾病仍不明确。通过定量聚合酶链反应（qPCR）分析了19597名40至69岁参与者的DNA，以检测iciHHV - 6的存在。通过qPCR测定端粒长度。比较了iciHHV - 6阳性和iciHHV - 6阴性受试者的病历、血液学、生化和人体测量数据以及端粒长度。iciHHV - 6的患病率为0.58%。采用经霍尔姆 - 邦费罗尼校正的双向方差分析来确定iciHHV - 6、性别及其相互作用对连续结果的影响。采用经霍尔姆 - 邦费罗尼校正的双向逻辑回归来确定iciHHV - 6、性别及其相互作用对疾病患病率的影响。在监测的50种疾病中，相对于iciHHV - 6阴性受试者，iciHHV - 6阳性个体中唯一一种疾病——心绞痛显著升高（3.3倍）（P = 0.017；95%置信区间，1.73 - 6.35）。在对潜在混杂因素（年龄、体重指数、体脂百分比和收缩压）进行调整后，iciHHV - 6阳性受试者中心绞痛的患病率仍高出三倍（P = 0.015；95%置信区间，1.23 - 7.15）。对无心绞痛的iciHHV - 6阴性、有心绞痛的iciHHV - 6阴性和有心绞痛的iciHHV - 6阳性个体的端粒长度分析表明，有心绞痛的iciHHV - 6阳性个体的端粒比年龄匹配的iciHHV - 6阴性受试者短（P = 0.006）。据我们所知，我们的研究是首次对与iciHHV - 6相关疾病进行的大规模分析。我们的结果与iciHHV - 6是心绞痛发生的一个危险因素一致。
