Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268

Michelle Cespedes, Sarah Kerns, Robert Holzman, Paul McLaren, Harry Ostrer, Judith Aberg

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Abstract

Objective: To examine genome-wide associations in HIV-infected women with a history of cervical dysplasia compared with HIV-infected women with no history of abnormal Papanicolaou (Pap) tests. Design: Case-control study using data from women analyzed for the HIV Controllers Study and enrolled in HIV treatment-naïve studies in the AIDS Clinical Trials Group (ACTG). Methods: Genotyping utilized Illumina HumanHap 650 Y or 1MDuo platforms. After quality control and principal component analysis, ~610,000 significant single nucleotide polymorphisms (SNPs) were tested for association. Threshold for significance was P < 5 × 10-8 for genome-wide associations. Results: No significant genomic association was observed between women with low-grade dysplasia and controls. The genome-wide association study (GWAS) analysis between women with high-grade dysplasia or invasive cervical cancer and normal controls identified significant SNPs. In the analyses limited to African American women, 11 SNPs were significantly associated with the development of high-grade dysplasia or cancer after correcting for multiple comparisons. The model using significant SNPs alone had improved accuracy in predicting high-grade dysplasia in African American women compared to the use of clinical data (area under the receiver operating characteristic curve for genetic and clinical model = 0.9 and 0.747, respectively). Conclusions: These preliminary data serve as proof of concept that there may be a genetic predisposition to developing high-grade cervical dysplasia in African American HIV-infected women. Given the small sample size, the results need to be validated in a separate cohort.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalHIV Clinical Trials
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2013

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Keywords

  • GWAS
  • cervical dysplasia
  • risk markers

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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