Abstract
BackgroundHIV-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.MethodsPatients 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.ResultsWe 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.ConclusionThe 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.
Highlights
Human immunodeficiency virus (HIV)-infected individuals have an increased risk of cardiovascular disease (CVD)
Our aims were 1) to explore the relationship between the CD14 C-260T single-nucleotide polymorphism (SNP) on markers of monocyte/macrophage activation (including soluble(s) CD14 and Soluble CD163 (sCD163)) and inflammation (as measured by highly sensitive C-reactive protein and 2) to assess the association between the CD14 C-260T SNP and subclinical atherosclerosis measured by carotid intima-media thickness
Cohort characteristics and distribution of CD14 (C-260T) SNP Patients were identified from a pre-existing study assessing the prevalence of metabolic syndrome and subclinical atherosclerosis among HIV-infected individuals on combination antiretroviral therapy (cART)
Summary
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. Persistent immune activation and inflammation have been well described in chronic HIV disease (reviewed in [1]) and have been associated with an increased risk of atherosclerosis in this population [2-6]. T vs C allele carriers have been found to have higher density of membranebound CD14 and circulating levels of sCD14 [18,19,22] and subsequent increased production of pro-inflammatory cytokines following LPS stimulation [19,21,23]. This in turn may influence the development and progression of atherosclerotic disease. Two non-synonymous SNPs in the TLR4 gene, Asp299Gly and Thr399Ile, have been associated with reduced cytokine responses following LPS stimulation in some studies [24,25] and the carriage of these SNPs may modulate LPS-mediated responses
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