title: Lack of association between polymorphisms in the interleukin-1 gene cluster and familial thrombophilia.
abstract: BACKGROUND
  Inflammation and venous thrombosis are intimately linked, and there is evidence that levels of inflammatory cytokines influence risk of venous thrombosis. We investigated the hypothesis that allelic variation within the IL-1 gene cluster, which encompasses the genes encoding the inflammatory cytokines IL-1α and IL-1β and the competitive IL-1 receptor antagonist, is associated with venous thrombosis among patients with heritable thrombophilia.
  
  
  METHODS
  Genomic DNA samples from 181 index cases with heritable thrombophilia and 323 control subjects were genotyped for four SNPs, and four microsatellite markers located within the IL-1 gene cluster. The distributions of SNP genotypes and of microsatellite marker alleles were then compared between the patient and control groups.
  
  
  RESULTS
  There was no significant difference in the distribution of alleles between the patients and control subjects for any of the four microsatellite loci studied. Likewise, the distribution of genotypes for each of the four SNPs investigated was similar among the cases and control subjects. Haplotype analysis showed no difference in the estimated frequencies of any of the IL-1 gene cluster haplotypes between the patients and control subjects.
  
  
  CONCLUSIONS
  Our findings in this study suggest that inherited variation within the IL-1 gene cluster is not associated with thrombosis among patients with heritable thrombophilia and that alterations in inflammatory cytokines encoded by loci in the IL-1 gene cluster are more likely to occur as a result, rather than a cause, of venous thrombosis.
authors.affiliation: Department of Cardiovascular Science, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Marsden
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
authors.forename: Mike
authors.initials: M
authors.lastname: Makris
authors.forename: Martina E
authors.initials: ME
authors.lastname: Daly
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D019851:Thrombophilia / Q000235:genetics*
chemical_list: D007375:Interleukin-1