A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F15%3A33154949" target="_blank" >RIV/61989592:15110/15:33154949 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/15:10295603

Result on the web

<a href="http://dx.doi.org/10.1093/hmg/ddv015" target="_blank" >http://dx.doi.org/10.1093/hmg/ddv015</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/hmg/ddv015" target="_blank" >10.1093/hmg/ddv015</a>

Result language

angličtina

Original language name

A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity.

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Human Molecular Genetics (print)

ISSN

0964-6906

e-ISSN

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Volume of the periodical

24

Issue of the periodical within the volume

9

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

2681-2688

UT code for WoS article

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EID of the result in the Scopus database

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