1284. Study of Single Nucleotide Polymorphisms Associated with HIV-1 Set-Point Viral Load in Antiretroviral Therapy-Naïve HIV-Positive Participants of the START Study
Poster Abstract Session: HIV: Molecular Epidemiology
Friday, October 5, 2018
Room: S Poster Hall
Background: HIV-1 set-point viral load (SPVL) is predictive of
disease progression and shows variability across HIV-1-positive (HIV+) persons.
Various factors may influence SPVL including viral features, environmental
exposure and host genetics. To identify single nucleotide polymorphisms (SNPs)
associated with SPVL, we performed a genome-wide association study (GWAS) on a
subset of participants from the Strategic Timing of AntiRetroviral Treatment (START) study covering a
demographically diverse population.
Methods: Consenting participants were antiretroviral
therapy (ART)-naïve and SPVL was taken as log10(HIV RNA) at study entry. Genotypic
data was generated on a custom content Affymetrix Axiom SNP array covering
770,558 probes. The Ensembl Gene database, assembly GRCh37.p13, was used for
annotation. Principal component analysis (PCA) was used to identify population
structures, and analysis of variance (ANOVA) was performed to detect
associations between SNPs and SPVL. SNPs with zero variance or minor allele
frequency (MAF) ≤0.05 were removed.
Results: Among the 2544 participants, PCA showed distinct population
structures with strong separation between black (n=578) and non-black (n=1966)
participants, Fig 1. ANOVA was performed independently on both subsets. Two
SNPs located in the Major Histocompatibility Complex (MHC) class I region of
chromosome 6 reached genome-wide significance (P < 5 x 10-8)
in the non-black population: rs4418214 (P = 1.74 x 10-10), and rs57989216 (P
= 3.96 x 10-8), Fig 2. Two additional SNPs, rs9264942 (P =
5.99 x 10-8) and rs7356880 (P = 9.69 x 10-8), in
the same region approached significance. The minor alleles of all four SNPs
were associated with lower SPVL, Fig 3. While no SNPs reached genome-wide
significance in the black group, we observed similar trends toward lower SPVL for
both rs4418214 and rs57989216.
Conclusion: In this study we confirm the association of a
previously reported SNP (rs4418214) and identify a novel candidate SNP (rs57989216)
associated with lower SPVL in a population of non-black, ART-naïve HIV+ persons.
Current findings suggest that the effects of these SNPs are consistent across
race groups, but further studies are required to confirm this. Our results support
previous findings that variation in the MHC class I region is a major host
determinant of HIV-1 control.
M. H. E. Tang,
D. D. Murray,
Centre of Excellence for Health, Immunity and Infectious diseases (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark:
B. T. Sherman,
J. M. Molina,
C. M. Kityo,
M. N. Polizzotto,
J. D. Neaton,
H. C. Lane,
J. D. Lundgren,
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