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HIV Clin Trials DOI:10.1310/hct1406-292

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

Publication TypeJournal Article
Year of Publication2013
AuthorsCespedes, MS, Kerns, SL, Holzman, RS, McLaren, PJ, Ostrer, H, Aberg, JA
JournalHIV Clin Trials
Volume14
Issue6
Pages292-302
Date Published2013 Nov-Dec
ISSN1528-4336
KeywordsAdult, African Americans, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotyping Techniques, HIV Infections, Humans, Logistic Models, Middle Aged, Papanicolaou Test, Polymorphism, Single Nucleotide, Quality Control, Uterine Cervical Dysplasia, Vaginal Smears
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

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.

URLhttp://thomasland.metapress.com/openurl.asp?genre=article&id=doi:10.1310/hct1406-292
DOI10.1310/hct1406-292
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24334182?dopt=Abstract

Alternate JournalHIV Clin Trials
PubMed ID24334182
PubMed Central IDPMC4118741
Grant ListL60 MD006511 / MD / NIMHD NIH HHS / United States
AI069532 / AI / NIAID NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
U01 AI069532 / AI / NIAID NIH HHS / United States
1UL1RR09893 / RR / NCRR NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069532 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States