The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals

Reena Rajasuriar, Yong Yean Kong, Reshika Nadarajah, Noor Kamila Abdullah, Tim Spelman, Muhamad Yazli Yuhana, Sasheela Ponampalavanar, Adeeba Kamarulzaman, Sharon R. Lewin

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Abstract

Background: HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals. Methods: Patients with no pre-existing CVD risk factors on suppressive antiretroviral therapy were recruited from University Malaya Medical Centre, Malaysia (n = 84). The CD14 C-260T and TLR4 SNPs, Asp299Gly and Thr399Ile were genotyped and soluble(s) CD14 and sCD163 and high-sensitivity C-reactive protein, hsCRP were measured in plasma. Subclinical atherosclerosis was assessed by measuring carotid intima media thickness (cIMT). The association between CD14 C-260T SNP carriage and cIMT was assessed in a multivariable quantile regression model where a p-value of <0.05 was considered significant. Results: We found the CD14 C-260T T-allele in 56% of the cohort and evidence of subclinical atherosclerosis in 27%. TT genotype was associated with higher sCD163 (p = 0.009) but only marginally higher sCD14 (p = 0.209) and no difference in hsCRP (p = 0.296) compared to CC/CT. In multivariable analysis, only Framingham risk score was independently associated with higher cIMT while lower sCD163 was trending towards significance. No association was found in TT-genotype carriers and cIMT measurements. Conclusion: The CD14 C-260T SNP was associated with increased monocyte activation but not systemic inflammation or cIMT in this HIV-infected cohort with low CVD risk profile.

Original languageEnglish
Article number30
JournalJournal of Translational Medicine
Volume13
Issue number30
DOIs
Publication statusPublished - 27 Jan 2015

Keywords

  • Atherosclerosis
  • C-reactive protein
  • Carotid intima media thickness
  • CD12 C-260T
  • HIV
  • Lipopolysaccharide
  • Monocyte activation
  • Soluble CD14
  • Soluble CD163

Cite this

Rajasuriar, R., Kong, Y. Y., Nadarajah, R., Abdullah, N. K., Spelman, T., Yuhana, M. Y., Ponampalavanar, S., Kamarulzaman, A., & Lewin, S. R. (2015). The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals. Journal of Translational Medicine, 13(30), [30]. https://doi.org/10.1186/s12967-015-0391-6