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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere99109
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 11 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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