Association of a 3' untranslated region polymorphism in proprotein convertase subtilisin/kexin type 9 with HIV viral load and CD4+ levels in HIV/hepatitis C virus coinfected women

AIDS. 2017 Nov 28;31(18):2483-2492. doi: 10.1097/QAD.0000000000001648.


Objective: To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection.

Design: Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study.

Methods: We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women.

Results: Six SNPs were associated with both HIV viral load and CD4 T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3' untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n = 408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P = 0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P = 0.76) women in adjusted analysis.

Conclusion: PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.

MeSH terms

  • 3' Untranslated Regions*
  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • Coinfection / genetics*
  • Coinfection / pathology
  • Cross-Sectional Studies
  • Female
  • HIV Infections / genetics*
  • HIV Infections / pathology
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Longitudinal Studies
  • Polymorphism, Single Nucleotide*
  • Proprotein Convertase 9 / genetics*
  • Viral Load*


  • 3' Untranslated Regions
  • PCSK9 protein, human
  • Proprotein Convertase 9