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

Genes Immun
Authors
Keywords
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.

Year of Publication
2015
Journal
Genes Immun
Volume
16
Issue
1
Pages
1-7
Date Published
2015 Jan-Feb
ISSN
1476-5470
URL
DOI
10.1038/gene.2014.51
PubMed ID
25297839
PubMed Central ID
PMC4308645
Links
Grant list
U01HG006379 / HG / NHGRI NIH HHS / United States
U01 HG006385 / HG / NHGRI NIH HHS / United States
U01 HG006375 / HG / NHGRI NIH HHS / United States
U01HG006375 / HG / NHGRI NIH HHS / United States
U01 HG004438 / HG / NHGRI NIH HHS / United States
U01HG006830 / HG / NHGRI NIH HHS / United States
U01 HG006382 / HG / NHGRI NIH HHS / United States
U19 HL065962 / HL / NHLBI NIH HHS / United States
R01 LM010685 / LM / NLM NIH HHS / United States
U01HG006382 / HG / NHGRI NIH HHS / United States
HG004438 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
U01 HG006389 / HG / NHGRI NIH HHS / United States
U01 HG006828 / HG / NHGRI NIH HHS / United States
U01 HG006380 / HG / NHGRI NIH HHS / United States
U01HG006388 / HG / NHGRI NIH HHS / United States
U01 HG006388 / HG / NHGRI NIH HHS / United States
U01 HG006378 / HG / NHGRI NIH HHS / United States
U01 HG006379 / HG / NHGRI NIH HHS / United States
HG004424 / HG / NHGRI NIH HHS / United States
U01HG006385 / HG / NHGRI NIH HHS / United States
U01HG006378 / HG / NHGRI NIH HHS / United States
U01HG006828 / HG / NHGRI NIH HHS / United States
U01HG006389 / HG / NHGRI NIH HHS / United States
U01 HG006830 / HG / NHGRI NIH HHS / United States