Title |
Polymorphism rs1385129 Within Glut1 Gene SLC2A1 Is Linked to Poor CD4+ T Cell Recovery in Antiretroviral-Treated HIV+ Individuals
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Published in |
Frontiers in immunology, May 2018
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DOI | 10.3389/fimmu.2018.00900 |
Pubmed ID | |
Authors |
Jesse J. R. Masson, Catherine L. Cherry, Nicholas M. Murphy, Isabel Sada-Ovalle, Tabinda Hussain, Riya Palchaudhuri, Jeffrey Martinson, Alan L. Landay, Baki Billah, Suzanne M. Crowe, Clovis S. Palmer |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 9 | 26% |
Australia | 6 | 17% |
Canada | 3 | 9% |
Switzerland | 2 | 6% |
United Kingdom | 2 | 6% |
Singapore | 2 | 6% |
Spain | 1 | 3% |
France | 1 | 3% |
Russia | 1 | 3% |
Other | 0 | 0% |
Unknown | 8 | 23% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 24 | 69% |
Scientists | 8 | 23% |
Science communicators (journalists, bloggers, editors) | 2 | 6% |
Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 6 | 16% |
Researcher | 5 | 13% |
Student > Bachelor | 4 | 11% |
Professor | 3 | 8% |
Other | 2 | 5% |
Other | 6 | 16% |
Unknown | 12 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 12 | 32% |
Agricultural and Biological Sciences | 5 | 13% |
Medicine and Dentistry | 4 | 11% |
Biochemistry, Genetics and Molecular Biology | 4 | 11% |
Nursing and Health Professions | 1 | 3% |
Other | 0 | 0% |
Unknown | 12 | 32% |