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Genes Immun. 2015 Jan-Feb;16(1):1-7. doi: 10.1038/gene.2014.51. Epub 2014 Oct 9.

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Author information

1
1] Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA [2] Department of Genome Sciences, University of Washington, Seattle, WA, USA.
2
Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
3
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
4
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
5
Department of Biostatistics, University of Washington, Seattle, WA, USA.
6
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
7
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
8
The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
9
1] Essentia Institute of Rural Health, Duluth, MN, USA [2] Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
10
Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
11
Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
12
Divisions of General Internal Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
13
Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
14
Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, Pennsylvania, PA, USA.
15
Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
16
1] Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA [2] Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
17
Division of General Internal Medicine, University of Washington, Seattle, WA, USA.
18
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine, New York, NY, USA.
19
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
20
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
21
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
22
Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA.
23
Cincinnati Children's Hospital Medical Center/Boston's Children's Hospital (CCHMC/BCH), Boston, MA, USA.

Abstract

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

PMID:
25297839
PMCID:
PMC4308645
DOI:
10.1038/gene.2014.51
[Indexed for MEDLINE]
Free PMC Article

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