title: CXCL16 haplotypes in patients with human carotid atherosclerosis: preliminary results.
abstract: OBJECTIVE
  Chemokine CXC ligand 16 (CXCL16) has chemoattractive, adhesive and scavenging properties and may play a role in the formation of atherosclerotic lesions. However, studies of CXCL16 polymorphisms in patients with atherosclerosis are scarce. The missense polymorphisms I123T and A181V are potentially important factors in the regulation of presentation and shedding of the CXCL16 chemokine domain. The aim of this study was to analyze the association between I123T and A181V polymorphism haplotypes and the accumulation of carotid plaque as well as the effect of the haplotype on the CXCL16 mRNA expression in carotid plaques in patients with advanced atherosclerosis. Additionally, we performed a bioinformatic prediction analysis of the impact of CXCL16 protein sequence variation on CXCL16-CXCR6 interactions and analyzed the soluble CXCL16 plasma levels according to the CXCL16 haplotype.
  
  
  METHODS
  This study evaluated a total of 733 participants, including 283 controls and 450 patients with carotid atherosclerosis (CA) undergoing endarterectomy. Analyses of the polymorphisms and the gene expression were performed using real-time PCR. The soluble CXCL16 levels were measured with ELISA.
  
  
  RESULTS
  The missense allele haplotype, T123V181, was found to be significantly and independently associated with the occurrence of CA plaque (OR=1.27;1.02-1.57, p=0.03). This haplotype was predicted to significantly change the CXCL16-CXCR6 interaction, compared to I123A181. Neither the CXCL16 mRNA expression in the human plaques nor the soluble CXCL16 plasma levels differed according to the haplotype.
  
  
  CONCLUSIONS
  These results indicate that the CXCL16 T123V181 haplotype is a moderate genetic risk factor for the development of carotid plaque. Further functional and replication studies are needed to clarify the mechanisms by which this combination of alleles promotes advanced CA and validate its impact on disease progression.
authors.affiliation: VINČA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade.
authors.forename: Maja
authors.initials: M
authors.lastname: Zivković
authors.forename: Tamara
authors.initials: T
authors.lastname: Djurić
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Stojković
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanović
authors.forename: Igor
authors.initials: I
authors.lastname: Končar
authors.forename: Lazar
authors.initials: L
authors.lastname: Davidović
authors.forename: Nevena
authors.initials: N
authors.lastname: Veljković
authors.forename: Dragan
authors.initials: D
authors.lastname: Alavantić
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanković
mesh_terms: D002340:Carotid Artery Diseases / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000097:blood / Q000235:genetics*; D051116:Receptors, Scavenger / Q000097:blood / Q000235:genetics*; D011991:Receptors, Virus / Q000097:blood / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D012333:RNA, Messenger; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus