title: Genetic polymorphisms in the CD14 gene are associated with monocyte activation and carotid intima-media thickness in HIV-infected patients on antiretroviral therapy.
abstract: HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). Given the relationship between innate immune activation and CVD, we investigated the association of single-nucleotide polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT), a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV-uninfected controls as a cross-sectional, case-control study. We quantified the frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38, HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for CD14/-260SNP but not the CC/CT genotype was associated with elevated plasma sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected individuals. The TT genotype was associated with lower cIMT in HIV-infected patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV-uninfected controls. SNPs in CD14/-260 and TLR4/+896 were significantly associated with different markers of systemic and monocyte activation and cIMT that differed between HIV-infected participants on ART and HIV-uninfected controls. Further investigation on the relationship of these SNPs with a clinical endpoint of CVD is warranted in HIV-infected patients on ART.
authors: Centre of Excellence for Research in AIDS (CERiA) Tropical Infectious Diseases Research and Education Centre (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Centre for Biomedical Research Centre for Population Health, Burnet Institute Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia Infectious Disease Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia Division of Infection Biology and Microbiology, Department of Life Sciences, School of Basic and Applied Sciences, Central University of Tamil Nadu (CUTN), Neelakudi Campus, Tiruvarur, India.
authors: Yean K
authors: YK
authors: Yong
authors: Esaki M
authors: EM
authors: Shankar
authors: Clare L V
authors: CLV
authors: Westhorpe
authors: Anna
authors: A
authors: Maisa
authors: Tim
authors: T
authors: Spelman
authors: Adeeba
authors: A
authors: Kamarulzaman
authors: Suzanne M
authors: SM
authors: Crowe
authors: Sharon R
authors: SR
authors: Lewin
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D039481:CD11b Antigen / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000097:blood; D019707:Receptors, Chemokine / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C111835:CCL2 protein, human; D039481:CD11b Antigen; D000098902:CD163 Antigen; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D018932:Chemokine CCL2; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D005340:Fibrinogen