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

Crosslin DR, Carrell DS, Burt A, Kim DS, Underwood JG, Hanna DS, Comstock BA, Baldwin E, de Andrade M, Kullo IJ, Tromp G, Kuivaniemi H, Borthwick KM, McCarty CA, Peissig PL, Doheny KF, Pugh E, Kho A, Pacheco J, Hayes MG, Ritchie MD, Verma SS, Armstrong G, Stallings S, Denny JC, Carroll RJ, Crawford DC, Crane PK, Mukherjee S, Bottinger E, Li R, Keating B, Mirel DB, Carlson CS, Harley JB, Larson EB, Jarvik GP - Genes Immun. (2014)

Bottom Line: 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)).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

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Manhattan plot of P-values generated using Cox regression analysis in the European ancestry sample.
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fig2: Manhattan plot of P-values generated using Cox regression analysis in the European ancestry sample.

Mentions: We provide the association results for herpes zoster association analyses stratified by genetically determined ancestry (Table 2). This included Cox regression analyses in the joint and European ancestry groups, as well as logistic regression analyses. Both the Cox and logistic regression models suggested a strong association on chromosome 6 in the human leukocyte antigen (HLA) region, specifically tagging HLA Complex P5 (HCP5) and upstream HLA-B in the beta block of the class 1 region (Figures 1 and 2, respectively).


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

Crosslin DR, Carrell DS, Burt A, Kim DS, Underwood JG, Hanna DS, Comstock BA, Baldwin E, de Andrade M, Kullo IJ, Tromp G, Kuivaniemi H, Borthwick KM, McCarty CA, Peissig PL, Doheny KF, Pugh E, Kho A, Pacheco J, Hayes MG, Ritchie MD, Verma SS, Armstrong G, Stallings S, Denny JC, Carroll RJ, Crawford DC, Crane PK, Mukherjee S, Bottinger E, Li R, Keating B, Mirel DB, Carlson CS, Harley JB, Larson EB, Jarvik GP - Genes Immun. (2014)

Manhattan plot of P-values generated using Cox regression analysis in the European ancestry sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308645&req=5

fig2: Manhattan plot of P-values generated using Cox regression analysis in the European ancestry sample.
Mentions: We provide the association results for herpes zoster association analyses stratified by genetically determined ancestry (Table 2). This included Cox regression analyses in the joint and European ancestry groups, as well as logistic regression analyses. Both the Cox and logistic regression models suggested a strong association on chromosome 6 in the human leukocyte antigen (HLA) region, specifically tagging HLA Complex P5 (HCP5) and upstream HLA-B in the beta block of the class 1 region (Figures 1 and 2, respectively).

Bottom Line: 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)).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus