Polymorphism rs1385129 Within Glutl Gene SLC2A1 Is Linked to Poor CD4+T Cell Recovery in Antiretroviral-Treated HIV plus Individuals
AuthorMasson, JJR; Cherry, CL; Murphy, NM; Sada-Ovalle, I; Hussain, T; Palchaudhuri, R; Martinson, J; Landay, AL; Billah, B; Crowe, SM; ...
Source TitleFrontiers in Immunology
PublisherFRONTIERS MEDIA SA
Microbiology and Immunology
Document TypeJournal Article
CitationsMasson, J. J. R., Cherry, C. L., Murphy, N. M., Sada-Ovalle, I., Hussain, T., Palchaudhuri, R., Martinson, J., Landay, A. L., Billah, B., Crowe, S. M. & Palmer, C. S. (2018). Polymorphism rs1385129 Within Glutl Gene SLC2A1 Is Linked to Poor CD4+T Cell Recovery in Antiretroviral-Treated HIV plus Individuals. FRONTIERS IN IMMUNOLOGY, 9 (MAY), https://doi.org/10.3389/fimmu.2018.00900.
Access StatusOpen Access
Untreated HIV infection is associated with progressive CD4+ T cell depletion, which is generally recovered with combination antiretroviral therapy (cART). However, a significant proportion of cART-treated individuals have poor CD4+ T cell reconstitution. We investigated associations between HIV disease progression and CD4+ T cell glucose transporter-1 (Glut1) expression. We also investigated the association between these variables and specific single nucleotide polymorphisms (SNPs) within the Glut1 regulatory gene AKT (rs1130214, rs2494732, rs1130233, and rs3730358) and in the Glut1-expressing gene SLC2A1 (rs1385129 and rs841853) and antisense RNA 1 region SLC2A1-AS1 (rs710218). High CD4+Glut1+ T cell percentage is associated with rapid CD4+ T cell decline in HIV-positive treatment-naïve individuals and poor T cell recovery in HIV-positive individuals on cART. Evidence suggests that poor CD4+ T cell recovery in treated HIV-positive individuals is linked to the homozygous genotype (GG) associated with SLC2A1 SNP rs1385129 when compared to those with a recessive allele (GA/AA) (odds ratio = 4.67; P = 0.04). Furthermore, poor response to therapy is less likely among Australian participants when compared against American participants (odds ratio: 0.12; P = 0.01) despite there being no difference in prevalence of a specific genotype for any of the SNPs analyzed between nationalities. Finally, CD4+Glut1+ T cell percentage is elevated among those with a homozygous dominant genotype for SNPs rs1385129 (GG) and rs710218 (AA) when compared to those with a recessive allele (GA/AA and AT/TT respectively) (P < 0.04). The heterozygous genotype associated with AKT SNP 1130214 (GT) had a higher CD4+Glut1+ T cell percentage when compared to the dominant homozygous genotype (GG) (P = 0.0068). The frequency of circulating CD4+Glut1+ T cells and the rs1385129 SLC2A1 SNP may predict the rate of HIV disease progression and CD4+ T cell recovery in untreated and treated infection, respectively.
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