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A systematic invest...
A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity
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- Chen, Dan (author)
- Uppsala universitet,Medicinsk genetik och genomik
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Gaborieau, Valerie (author)
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Zhao, Yao (author)
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Chabrier, Amelie (author)
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Wang, Huibo (author)
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Waterboer, Tim (author)
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Zaridze, David (author)
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Lissowska, Jolanta (author)
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Rudnai, Peter (author)
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Fabianova, Eleonora (author)
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Bencko, Vladimir (author)
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Janout, Vladimir (author)
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Foretova, Lenka (author)
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Mates, Ioan Nicolae (author)
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Szeszenia-Dabrowska, Neonila (author)
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Boffetta, Paolo (author)
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Pawlita, Michael (author)
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Lathrop, Mark (author)
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- Gyllensten, Ulf (author)
- Uppsala universitet,Medicinsk genetik och genomik
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Brennan, Paul (author)
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McKay, James D. (author)
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(creator_code:org_t)
- 2015-01-23
- 2015
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:9, s. 2681-2688
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- High-risk mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected to be involved in non-melanoma skin cancer. The antibody response to HPVs is a key determinant of protective immunity, but not all infected individuals seroconvert. Genetic variability of the host may have large impact on seroconversion. A previous genome-wide association study (GWAS) has identified a susceptibility locus (rs41270488) for HPV8 seropositivity within the major histocompatibility complex (MHC) region. To further study this locus, we imputed alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted an integrated analysis among 4811 central European subjects to assess the contribution of classical HLA alleles and gene copy number variation (CNV) at the hypervariable DRB locus within the MHC region to HPV seropositivity at both the individual HPV type level and the phylogenetic species level. Our study provides evidence that the association noted between rs41270488 and HPV8 seropositivity is driven by two independent variants, namely DQB1*0301 [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.36-1.68, P = 1.0 x 10(-14)] and DRB1*1101 (OR = 1.89, 95% CI = 1.57-2.28, P = 1.5 x 10(-11)) within the HLA class II region. Additionally, we identified two correlated alleles DRB1*0701 (OR = 1.67, 95% CI = 1.41-1.98, P = 2.6 x 10(-9)) and DQA1*0201 (OR = 1.67, 95% CI = 1.38-1.93, P = 1.7 x 10(-8)), to be associated with HPV77 seropositivity. Comparable results were observed through imputation using SNP2HLA with another reference panel from the Type 1 diabetes Genetics Consortium. This study provides support for an important role of HLA class II alleles in antibody response to HPV infection.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Chen, Dan
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Gaborieau, Valer ...
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Zhao, Yao
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Chabrier, Amelie
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Wang, Huibo
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Waterboer, Tim
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show more...
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Zaridze, David
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Lissowska, Jolan ...
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Rudnai, Peter
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Fabianova, Eleon ...
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Bencko, Vladimir
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Janout, Vladimir
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Foretova, Lenka
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Mates, Ioan Nico ...
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Szeszenia-Dabrow ...
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Boffetta, Paolo
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Pawlita, Michael
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Lathrop, Mark
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Gyllensten, Ulf
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Brennan, Paul
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McKay, James D.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Human Molecular ...
- By the university
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Uppsala University