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Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter
Published on: March 31, 2022
Copy Number Variation within Human β-Defensin Gene Cluster Influences Progression to AIDS in the Multicenter AIDS
Rajeev K Mehlotra1, Jean-Eudes Dazard, Bangan John
1Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Study Background:
DEFB4/103A encoding β-defensin 2 and 3, respectively, inhibit CXCR4-tropic (X4) viruses in vitro. We determined whether DEFB4/103A Copy Number Variation (CNV) influences time-to-X4 and time-to-AIDS outcomes.
Methods:
We utilized samples from a previously published Multicenter AIDS Cohort Study (MACS), which provides longitudinal account of viral tropism in relation to the full spectrum of rates of disease progression. Using traditional models for time-to-event analysis, we investigated association between DEFB4/103A CNV and the two outcomes, and interaction between DEFB4/103A CNV and disease progression groups, Fast and Slow.
Results:
Time-to-X4 and time-to-AIDS were weakly correlated. There was a stronger relationship between these two outcomes for the fast progressors. DEFB4/103A CNV was associated with time-to-AIDS, but not time-to-X4. The association between higher DEFB4/103A CNV and time-to-AIDS was more pronounced for the slow progressors.
Conclusion:
DEFB4/103A CNV was associated with time-to-AIDS in a disease progression group-specific manner in the MACS cohort. Our findings may contribute to enhancing current understanding of how genetic predisposition influences AIDS progression.
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