title: Interferon-induced transmembrane protein-3 rs12252-C is associated with rapid progression of acute HIV-1 infection in Chinese MSM cohort.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China.
authors.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.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shokouh
authors.initials: S
authors.lastname: Makvandi-Nejad
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Emmanouela
authors.initials: E
authors.lastname: Repapi
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D000068476:Beijing; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D019562:Viral Load; D014766:Viremia / Q000235:genetics*; D055815:Young Adult
chemical_list: C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins