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

• Published in: PloS one Vol. 9; no. 6; p. e99109
• Main Authors: Sudenga, Staci L, Wiener, Howard W, King, Caroline C, Rompalo, Anne M, Cu-Uvin, Susan, Klein, Robert S, Shah, Keerti V, Sobel, Jack D, Jamieson, Denise J, Shrestha, Sadeep
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.06.2014; Public Library of Science (PLoS)
• Subjects: African Americans; Analysis; Antigens; Biology and Life Sciences; CD4 antigen; Cervical cancer; Cervix; Deoxyribonucleic acid; Disease control; Disease prevention; DNA; DNA microarrays; DNA, Viral - genetics; DNA, Viral - isolation & purification; Epidemiology; Female; Genetic factors; Genomes; Genotype; Genotyping; Hazards; Health risks; Histocompatibility antigen HLA; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV patients; HLA antigens; Human immunodeficiency virus; Human papillomavirus; Humans; Hybridization; Immune clearance; Immune response; Immune system; Infection; Infections; Loci; Mathematical models; Medicine; Medicine and Health Sciences; Minority & ethnic groups; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Pathogenesis; Polymorphism; Proteins; Race; Reproductive health; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Smad3 protein; Statistical models; Studies; Womens health; Atlanta Georgia; New York; United States > US; Georgia; Alabama; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0099109

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.