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A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity
D. Chen, V. Gaborieau, Y. Zhao, A. Chabrier, H. Wang, T. Waterboer, D. Zaridze, J. Lissowska, P. Rudnai, E. Fabianova, V. Bencko, V. Janout, L. Foretova, IN. Mates, N. Szeszenia-Dabrowska, P. Boffetta, M. Pawlita, M. Lathrop, U. Gyllensten, P....
Language English Country England, Great Britain
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1996 to 1 year ago
Open Access Digital Library
from 1996-01-01
PubMed
25616963
DOI
10.1093/hmg/ddv015
Knihovny.cz E-resources
- MeSH
- Alleles * MeSH
- Genetic Predisposition to Disease * MeSH
- Genetic Variation * MeSH
- Haplotypes MeSH
- HLA Antigens genetics MeSH
- Major Histocompatibility Complex genetics MeSH
- Papillomavirus Infections genetics virology MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Odds Ratio MeSH
- Papillomaviridae classification genetics MeSH
- Case-Control Studies MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
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 × 10(-14)] and DRB1*1101 (OR = 1.89, 95%CI = 1.57-2.28, P = 1.5 × 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 × 10(-9)) and DQA1*0201 (OR = 1.67, 95%CI = 1.38-1.93, P = 1.7 × 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.
Centre D'innovation Génome Québec et Université McGill Montréal Canada
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Epidemiology Institute of Occupational Medicine Lodz Poland
Department of Neurosurgery 1st Affiliated Hospital of Nanjing Medical University Nanjing China
Department of Neurosurgery Huashan Hospital Shanghai Medical School Fudan University Shanghai China
Genetic Cancer Susceptibility Group International Agency for Research on Cancer Lyon France
Infections and Cancer Epidemiology Group Division of Genome Modifications and Carcinogenesis
Institute of Carcinogenesis Cancer Research Centre Moscow Russia
Mount Sinai Hospital Icahn Medical Institute New York USA and
National Institute of Environmental Health Budapest Hungary
Palacky University Olomouc Czech Republic
Regional Authority of Public Health Banská Bystrica Slovakia
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