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e-Article

Genetic variation in the HLA region is associated with susceptibility to herpes zoster
Document Type
article
Source
Genes & Immunity. 16(1)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Genetics
Immunology
HIV/AIDS
Human Genome
Infectious Diseases
Biotechnology
Aetiology
2.1 Biological and endogenous factors
Infection
Age of Onset
Aged
Algorithms
Cohort Studies
Electronic Health Records
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Herpes Zoster
Herpesvirus 3
Human
Humans
Male
Middle Aged
RNA
Long Noncoding
RNA
Untranslated
Retrospective Studies
United States
Language
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.