Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

Infect Genet Evol. 2016 Jul;41:185-190. doi: 10.1016/j.meegid.2016.03.037. Epub 2016 Apr 12.

Abstract

Aims: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).

Material and methods: We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.

Results: The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.

Conclusions: The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.

Keywords: Disease progression; HIV; Host genetics; Immune reconstitution; Viral load.

MeSH terms

  • Adult
  • Alleles
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • Denmark
  • Female
  • Gene Expression
  • Gene Frequency
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / growth & development
  • HLA-C Antigens / genetics*
  • HLA-C Antigens / immunology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / immunology
  • Viral Load / drug effects
  • Viral Load / genetics*
  • Viral Load / immunology

Substances

  • Anti-Retroviral Agents
  • DNA-Binding Proteins
  • HCP5 long noncoding RNA, human
  • HLA-C Antigens
  • RNA, Long Noncoding
  • RNA, Untranslated
  • ZNRD1 protein, human