Dense genotyping of immune-related loci identifies variants associated with clearance of HPV among HIV-positive women in the HIV epidemiology research study (HERS)

Staci L Sudenga; Howard W Wiener; Caroline C King; Anne M Rompalo; Susan Cu-Uvin; Robert S Klein; Keerti V Shah; Jack D Sobel; Denise J Jamieson; Sadeep Shrestha

doi:10.1371/journal.pone.0099109

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Dense genotyping of immune-related loci identifies variants associated with clearance of HPV among HIV-positive women in the HIV epidemiology research study (HERS)

Journal article

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Dense genotyping of immune-related loci identifies variants associated with clearance of HPV among HIV-positive women in the HIV epidemiology research study (HERS)

Staci L Sudenga, Howard W Wiener, Caroline C King, Anne M Rompalo, Susan Cu-Uvin, Robert S Klein, Keerti V Shah, Jack D Sobel, Denise J Jamieson and Sadeep Shrestha

PloS one, Vol.9(6), pp.e99109-e99109

06/11/2014

DOI: 10.1371/journal.pone.0099109

PMCID: PMC4053382

PMID: 24918582

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Abstract

Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance (p<10(-6)). A variant (rs1633038) in HLA-G were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes.

DNA, Viral - genetics

DNA, Viral - isolation & purification

Female

Genotype

HIV Infections - genetics

HIV Infections - immunology

HIV Infections - virology

Humans

Papillomaviridae - genetics

Papillomaviridae - isolation & purification

Details

Title: Subtitle: Dense genotyping of immune-related loci identifies variants associated with clearance of HPV among HIV-positive women in the HIV epidemiology research study (HERS)
Creators: Staci L Sudenga - University of Alabama at Birmingham
Howard W Wiener - University of Alabama at Birmingham
Caroline C King - Centers for Disease Control and Prevention
Anne M Rompalo - Johns Hopkins Medicine
Susan Cu-Uvin - Brown University
Robert S Klein - Icahn School of Medicine at Mount Sinai
Keerti V Shah - Johns Hopkins University
Jack D Sobel - Wayne State University
Denise J Jamieson - Centers for Disease Control and Prevention
Sadeep Shrestha - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: PloS one, Vol.9(6), pp.e99109-e99109
DOI: 10.1371/journal.pone.0099109
PMID: 24918582
PMCID: PMC4053382
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: P50 CA098252 / NCI NIH HHS U64/CCU106795 / PHS HHS U64/CCU306802 / PHS HHS 2P50CA098252 / NCI NIH HHS R25 CA047888 / NCI NIH HHS U64/CCU206798 / PHS HHS U64/CCU506831 / PHS HHS R25CA47888 / NCI NIH HHS
Language: English
Date published: 06/11/2014
Academic Unit: Obstetrics and Gynecology; VPMA - Administration
Record Identifier: 9984446547502771

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