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

• Published in: Genes and immunity Vol. 16; no. 1; pp. 1 - 7
• Main Authors: Crosslin, D R, Carrell, D S, Burt, A, Kim, D S, Underwood, J G, Hanna, D S, Comstock, B A, Baldwin, E, de Andrade, M, Kullo, I J, Tromp, G, Kuivaniemi, H, Borthwick, K M, McCarty, C A, Peissig, P L, Doheny, K F, Pugh, E, Kho, A, Pacheco, J, Hayes, M G, Ritchie, M D, Verma, S S, Armstrong, G, Stallings, S, Denny, J C, Carroll, R J, Crawford, D C, Crane, P K, Mukherjee, S, Bottinger, E, Li, R, Keating, B, Mirel, D B, Carlson, C S, Harley, J B, Larson, E B, Jarvik, G P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2015; Nature Publishing Group
• Subjects: 45; 45/43; 631/208/205/2138; 631/208/726/649; 631/250/255/2514; Age of Onset; Aged; Algorithms; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cohort Studies; Disease susceptibility; Electronic Health Records; Female; Gene Expression; Genetic aspects; Genetic Predisposition to Disease; Genetic variation; Genome-Wide Association Study; Herpes Zoster - epidemiology; Herpes Zoster - ethnology; Herpes Zoster - genetics; Herpes Zoster - immunology; Herpesvirus 3, Human - physiology; Histocompatibility antigens; HLA histocompatibility antigens; Human Genetics; Human immunodeficiency virus; Humans; Immunology; Male; Middle Aged; Original; original-article; Physiological aspects; Retrospective Studies; RNA, Long Noncoding; RNA, Untranslated - genetics; Shingles (Disease); United States - epidemiology; United States - ethnology; Varicella-zoster virus; United States
• ISSN: 1466-4879; 1476-5470; 1476-5470
• DOI: 10.1038/gene.2014.51

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.