title: Severity of coronary artery stenosis is associated with a polymorphism in the CXCL16/SR-PSOX gene.
abstract: OBJECTIVE
  Enhanced expression of CXCL16 has been demonstrated in atherosclerotic plaques and several properties have been attributed to CXCL16 that could influence the atherosclerotic process. CXCL16 exists in transmembrane and soluble forms. The transmembrane form acts as a scavenger receptor for oxidised LDL whereas the soluble form acts a chemoattractant for mainly CD8+ T cells. In addition, the soluble form of CXCL16 influences human aortic smooth muscle cell proliferation in vitro. In the present work, a human molecular genetic approach employing a common polymorphism within exon 4 of CXCL16 (181 Ala>Val) was used to investigate whether CXCL16 may be involved in the development of coronary artery disease. The polymorphism is located within the spacer region between the chemokine and transmembrane region and potentially influences an Ala/Val cleavage site, a site commonly used for the release of chemokines by tumour necrosis factor-alpha converting enzyme.
  
  
  METHODS
  We first genotyped 387 unselected survivors of a first myocardial infarction aged <60 years and 387 sex- and age-matched controls. A subset of patients (n = 236) was evaluated by quantitative coronary angiography. Secondly, a cohort of 468 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with stent implantation was genotyped.
  
  
  RESULTS
  No significant difference in allele frequency between patient and controls of the 181 A>V polymorphism was detected. However, the V-allele was associated with increased severity of coronary stenoses. Secondly, the V-allele was associated with smaller minimal luminal diameter in the coronary segment subjected to intervention in a second cohort of patients undergoing PTCA with stent implantation.
  
  
  CONCLUSIONS
  The present work provides evidence that CXCL16 is involved in processes leading to enhanced stenosis in atherosclerotic coronary arteries.
authors.affiliation: Department of Caring Sciences, Biomedicine, Orebro University, Orebro, Sweden. gunilla.lundberg@ivo.oru.se <gunilla.lundberg@ivo.oru.se>
authors.forename: G A
authors.initials: GA
authors.lastname: Lundberg
authors.forename: A
authors.initials: A
authors.lastname: Kellin
authors.forename: A
authors.initials: A
authors.lastname: Samnegård
authors.forename: P
authors.initials: P
authors.lastname: Lundman
authors.forename: P
authors.initials: P
authors.lastname: Tornvall
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: A
authors.initials: A
authors.lastname: Hamsten
authors.forename: G K
authors.initials: GK
authors.lastname: Hansson
authors.forename: P
authors.initials: P
authors.lastname: Eriksson
mesh_terms: D000595:Amino Acid Sequence; D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary; D016022:Case-Control Studies; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051116:Receptors, Scavenger; D017422:Sequence Analysis, DNA; D015607:Stents
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger