title: The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. reena@um.edu.my.|Centre of Excellence for Research in AIDS (CERiA), University of Malaya, 50603, Kuala Lumpur, Malaysia. reena@um.edu.my.|Department of Infectious Diseases, Monash University and Alfred Hospital, 3004, Melbourne, Australia. reena@um.edu.my.
authors.forename: Reena
authors.initials: R
authors.lastname: Rajasuriar
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, 50603, Kuala Lumpur, Malaysia. yong.yeankong@gmail.com.
authors.forename: Yong Yean
authors.initials: YY
authors.lastname: Kong
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, 50603, Kuala Lumpur, Malaysia. n.reshika@gmail.com.
authors.forename: Reshika
authors.initials: R
authors.lastname: Nadarajah
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, 50603, Kuala Lumpur, Malaysia. la_falcon00@yahoo.com.
authors.forename: Noor Kamila
authors.initials: NK
authors.lastname: Abdullah
authors.affiliation: Centre for Population Health, Burnet Institute, 3004, Melbourne, Australia. tim@burnet.edu.au.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. aleeyuhana@hotmail.com.|Faculty of Medicine, University Teknologi MARA, 47000, Sungai Buloh, Selangor, Malaysia. aleeyuhana@hotmail.com.
authors.forename: Muhamad Yazli
authors.initials: MY
authors.lastname: Yuhana
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, 50603, Kuala Lumpur, Malaysia. sasheela@gmail.com.|Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. sasheela@gmail.com.
authors.forename: Sasheela
authors.initials: S
authors.lastname: Ponampalavanar
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, 50603, Kuala Lumpur, Malaysia. adeeba@ummc.edu.my.|Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. adeeba@ummc.edu.my.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Department of Infectious Diseases, Monash University and Alfred Hospital, 3004, Melbourne, Australia. sharon.lewin@unimelb.edu.au.|Centre for Biomedical Research, Burnet Institute, 3004, Melbourne, Australia. sharon.lewin@unimelb.edu.au.|Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, 3010, Australia. sharon.lewin@unimelb.edu.au.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors