ArticleHIV clinical trials
Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268.
Article in HIV clinical trials. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
Funding
Abstract
objectiveTo 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.
designCase-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).
methodsGenotyping 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.
resultsNo 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).
conclusionsThese 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.
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