Polymorphism rs1385129 Within Glut1 Gene SLC2A1 Is Linked to Poor CD4+ T Cell Recovery in Antiretroviral-Treated HIV+ Individuals

Frontiers in Immunology

Clovis S. Palmer¹  Jesse J. R. Masson²  Riya Palchaudhuri²  Tabinda Hussain³  Jeffrey Martinson⁴  Alan L. Landay⁴  Suzanne M. Crowe⁵  Catherine L. Cherry⁶  Nicholas M. Murphy⁸  Baki Billah⁹  Isabel Sada-Ovalle^1,10 

[1] 0Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia;Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia;Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia;Department of Immunology-Microbiology, Rush University Medical Centre, Chicago, IL, United States;Department of Infectious Diseases, Monash University, Melbourne, VIC, Australia;Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia;Preimplantation Genetic Diagnosis, Monash IVF, Melbourne, VIC, Australia;School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia;Unidad de Investigación Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico;

关键词: HIV;    CD4+ T cells;    immune reconstitution;    immunometabolism;    Glut1;    AKT;   

DOI  :  10.3389/fimmu.2018.00900

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown