PMID- 26080419
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20240414
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 112
IP  - 26
DP  - 2015 Jun 30
TI  - Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk 
      factor for the development of angina pectoris.
PG  - 8058-63
LID - 10.1073/pnas.1502741112 [doi]
AB  - 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.
FAU - Gravel, Annie
AU  - Gravel A
AD  - Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire 
      (CHU) de Quebec-Universite Laval, Quebec City, QC, Canada G1V 4G2;
FAU - Dubuc, Isabelle
AU  - Dubuc I
AD  - Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire 
      (CHU) de Quebec-Universite Laval, Quebec City, QC, Canada G1V 4G2;
FAU - Morissette, Guillaume
AU  - Morissette G
AD  - Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire 
      (CHU) de Quebec-Universite Laval, Quebec City, QC, Canada G1V 4G2;
FAU - Sedlak, Ruth H
AU  - Sedlak RH
AD  - Molecular Virology Laboratory, Department of Laboratory Medicine, University of 
      Washington, Seattle, WA 98102;
FAU - Jerome, Keith R
AU  - Jerome KR
AD  - 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;
FAU - Flamand, Louis
AU  - Flamand L
AD  - Division of Infectious Disease and Immunity, Centre Hospitalier Universitaire 
      (CHU) de Quebec-Universite Laval, Quebec City, QC, Canada G1V 4G2; Department of 
      Microbiology, Infectious Disease and Immunology, Faculty of Medicine, Universite 
      Laval, Quebec City, QC, Canada G1V 0A6 louis.flamand@crchul.ulaval.ca.
LA  - eng
GR  - MOP_123214/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150615
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angina Pectoris/genetics/*virology
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Herpesvirus 6, Human/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Telomere
PMC - PMC4491735
OTO - NOTNLM
OT  - HHV-6
OT  - angina
OT  - chromosomal integration
OT  - ciHHV-6
OT  - telomere
COIS- The authors declare no conflict of interest.
EDAT- 2015/06/17 06:00
MHDA- 2015/11/18 06:00
PMCR- 2015/12/30
CRDT- 2015/06/17 06:00
PHST- 2015/06/17 06:00 [entrez]
PHST- 2015/06/17 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
PHST- 2015/12/30 00:00 [pmc-release]
AID - 1502741112 [pii]
AID - 201502741 [pii]
AID - 10.1073/pnas.1502741112 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):8058-63. doi: 
      10.1073/pnas.1502741112. Epub 2015 Jun 15.