title: Contribution of putative genetic factors and candidate gene variants to inter-individual variation of circulating fractalkine (CX3CL1) levels in a large UK twins' sample.
abstract: OBJECTIVE
  Soluble fractalkine (sFRACT) is involved in the pathogenesis of several clinical diseases. Our major objective was to determine to what extent its variation is governed by genetic factors and whether this genetic variation could be attributable to SNPs in five candidate genes: CX3CL1, CX3CR1, ADAM10, ADAM17 and AREG.
  
  
  METHODS
  Plasma levels of sFRACT and 38 SNPs, with minor allele frequency >0.1 were examined in a large twin sample drawn from the general UK population. The discovery sample included 3306 middle-aged females: 1172 MZ twins and 2134 DZ twins. A replication sample of 1675 twins was used to validate the major association results obtained in genetic association analysis in the discovery sample. We implemented variance component analysis to estimate contribution of putative genetic, (including above SNPs) and environmental factors to sFRACT variation.
  
  
  RESULTS
  sFRACT was found not to vary with either age or BMI. Putative genetic factors (heritability) explained 43.6±3% of the total variation of plasma sFRACT levels. However, we found no evidence of association between sFRACT and any of the examined SNPs, despite having >85% power to detect an association of just 1% of the variance explained. The results in the discovery and replication samples were in good agreement suggesting these findings are real.
  
  
  CONCLUSIONS
  Our results suggest involvement of genetic factors to inter-individual variation of sFRACT levels in a general human population. However, further studies are required to determine genetic polymorphisms affecting sFRACT variation.
authors.affiliation: Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Israel. Lyranf@gmail.com
authors.forename: Liran
authors.initials: L
authors.lastname: Franco
authors.forename: Frances M K
authors.initials: FM
authors.lastname: Williams
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trofimov
authors.forename: Gabriela
authors.initials: G
authors.lastname: Surdulescu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Gregory
authors.initials: G
authors.lastname: Livshits
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D000704:Analysis of Variance; D015992:Body Mass Index; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000097:blood* / Q000235:genetics*; D066255:EGF Family of Proteins; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019707:Receptors, Chemokine / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D006113:United Kingdom; D055815:Young Adult
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human