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Interferon-induced transmembrane protein-3 rs12252-C is associated with rapid progression of acute HIV-1 infection in Chinese MSM cohort.

Zhang Y, Makvandi-Nejad S, Qin L, Zhao Y, Zhang T, Wang L, Repapi E, Taylor S, McMichael A, Li N, Dong T, Wu H - AIDS (2015)

Bottom Line: The interferon-inducible transmembrane protein-3 (IFITM3) is a protein that restricts multiple pathogenic viruses such as influenza virus.The single-nucleotide polymorphism rs12252-C, which is rare in Caucasian populations, but much more common in the Han Chinese population, has been found in much higher homozygous frequency in patients with severe acute influenza.A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China.

View Article: PubMed Central - PubMed

Affiliation: aBeijing You'an Hospital, Capital Medical University, Beijing, China bCAMS -Oxford University Joint International Centre for Translational Immunology, Nuffield and Radcliffe Departments of Medicine, University of Oxford cMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University dThe Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK. *Hao Wu, Shokouh Makvandi-Nejad, Ning Li, Tao Dong, and Yonghong Zhang contributed equally to the writing of this article.

ABSTRACT

Background: The interferon-inducible transmembrane protein-3 (IFITM3) is a protein that restricts multiple pathogenic viruses such as influenza virus. The single-nucleotide polymorphism rs12252-C, which is rare in Caucasian populations, but much more common in the Han Chinese population, has been found in much higher homozygous frequency in patients with severe acute influenza. Until now, there has been no study on the effect of this genetic variant on the clinical control of other viral infections.

Objectives: To investigate the impact of IFITM3-rs12252 genotypes on primary HIV-1 infection progression in an acute HIV-1-infected cohort in Beijing (PRIMO), China.

Design and methods: We identified IFITM3-rs12252 genotypes of 178 acute HIV-1-infected patients and 196 HIV-negative candidates from the PRIMO cohort. HIV-1 viral load and CD4(+) T-cell counts were monitored at multiple time points during the first year of infection, and the association between IFITM3-rs12252 genotype and disease progression was evaluated.

Results: The current study shows that the IFITM3-rs12252 genetic variant affects the progression of HIV-1 infection, but not the acquisition. A significantly higher frequency of the CC/CT genotypes was found in rapid progressors compared to nonprogressors. Patients with CC/CT genotypes showed an elevated peak viremia level and significantly lower CD4(+) T-cell count at multiple time points during the first year of primary infection, and a significantly higher risk of rapid decline of the CD4(+) T-cell count to below 350  cells/μl.

Conclusion: A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China.

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C allele at IFITM3-rs12252 associated with rapid progression of acute HIV-1 infected patients.
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Figure 1: C allele at IFITM3-rs12252 associated with rapid progression of acute HIV-1 infected patients.

Mentions: At peak viremia, the viral load was significantly higher in CC/CT carriers, compared to TT genotype carriers (5.624 ± 0.114 vs. 4.962 ± 0.260; P = 0.010; Fig. 1a). However, there was no significant difference in the viral load levels between CC/CT and TT genotype carriers at initial infection and at viral set point. Both heterozygotes and homozygotes for C allele showed significantly lower CD4+ T-cell counts than homozygotes for the T allele, at the seroconversion time point (485.2 ± 15.33 vs. 563.0 ± 34.54; P = 0.0276), to the third (494.9 ± 14.78 vs. 576.0 ± 27.78; P = 0.0197), sixth (458.1 ± 14.58 vs. 566.7 ± 43.37; P = 0.0232), and at 12 months (418.3 ± 14.80 vs. 492.0 ± 32.64; P = 0.0324) after acute HIV-1 infection (Fig. 1b). To identify whether there is a difference in disease progression in individuals with CD4+ T-cell counts below 350, who are CC/CT genotypes carries versus the TT genotype carriers, a log-rank (Mantel–Cox) test was performed. The result of this test verified that CC/CT genotype carriers are more likely to become rapid progressors (P = 0.0068; Fig. 1c).


Interferon-induced transmembrane protein-3 rs12252-C is associated with rapid progression of acute HIV-1 infection in Chinese MSM cohort.

Zhang Y, Makvandi-Nejad S, Qin L, Zhao Y, Zhang T, Wang L, Repapi E, Taylor S, McMichael A, Li N, Dong T, Wu H - AIDS (2015)

C allele at IFITM3-rs12252 associated with rapid progression of acute HIV-1 infected patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4442129&req=5

Figure 1: C allele at IFITM3-rs12252 associated with rapid progression of acute HIV-1 infected patients.
Mentions: At peak viremia, the viral load was significantly higher in CC/CT carriers, compared to TT genotype carriers (5.624 ± 0.114 vs. 4.962 ± 0.260; P = 0.010; Fig. 1a). However, there was no significant difference in the viral load levels between CC/CT and TT genotype carriers at initial infection and at viral set point. Both heterozygotes and homozygotes for C allele showed significantly lower CD4+ T-cell counts than homozygotes for the T allele, at the seroconversion time point (485.2 ± 15.33 vs. 563.0 ± 34.54; P = 0.0276), to the third (494.9 ± 14.78 vs. 576.0 ± 27.78; P = 0.0197), sixth (458.1 ± 14.58 vs. 566.7 ± 43.37; P = 0.0232), and at 12 months (418.3 ± 14.80 vs. 492.0 ± 32.64; P = 0.0324) after acute HIV-1 infection (Fig. 1b). To identify whether there is a difference in disease progression in individuals with CD4+ T-cell counts below 350, who are CC/CT genotypes carries versus the TT genotype carriers, a log-rank (Mantel–Cox) test was performed. The result of this test verified that CC/CT genotype carriers are more likely to become rapid progressors (P = 0.0068; Fig. 1c).

Bottom Line: The interferon-inducible transmembrane protein-3 (IFITM3) is a protein that restricts multiple pathogenic viruses such as influenza virus.The single-nucleotide polymorphism rs12252-C, which is rare in Caucasian populations, but much more common in the Han Chinese population, has been found in much higher homozygous frequency in patients with severe acute influenza.A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China.

View Article: PubMed Central - PubMed

Affiliation: aBeijing You'an Hospital, Capital Medical University, Beijing, China bCAMS -Oxford University Joint International Centre for Translational Immunology, Nuffield and Radcliffe Departments of Medicine, University of Oxford cMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University dThe Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK. *Hao Wu, Shokouh Makvandi-Nejad, Ning Li, Tao Dong, and Yonghong Zhang contributed equally to the writing of this article.

ABSTRACT

Background: The interferon-inducible transmembrane protein-3 (IFITM3) is a protein that restricts multiple pathogenic viruses such as influenza virus. The single-nucleotide polymorphism rs12252-C, which is rare in Caucasian populations, but much more common in the Han Chinese population, has been found in much higher homozygous frequency in patients with severe acute influenza. Until now, there has been no study on the effect of this genetic variant on the clinical control of other viral infections.

Objectives: To investigate the impact of IFITM3-rs12252 genotypes on primary HIV-1 infection progression in an acute HIV-1-infected cohort in Beijing (PRIMO), China.

Design and methods: We identified IFITM3-rs12252 genotypes of 178 acute HIV-1-infected patients and 196 HIV-negative candidates from the PRIMO cohort. HIV-1 viral load and CD4(+) T-cell counts were monitored at multiple time points during the first year of infection, and the association between IFITM3-rs12252 genotype and disease progression was evaluated.

Results: The current study shows that the IFITM3-rs12252 genetic variant affects the progression of HIV-1 infection, but not the acquisition. A significantly higher frequency of the CC/CT genotypes was found in rapid progressors compared to nonprogressors. Patients with CC/CT genotypes showed an elevated peak viremia level and significantly lower CD4(+) T-cell count at multiple time points during the first year of primary infection, and a significantly higher risk of rapid decline of the CD4(+) T-cell count to below 350  cells/μl.

Conclusion: A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China.

Show MeSH
Related in: MedlinePlus