Lack of association between polymorphisms in the interleukin-1 gene cluster and familial thrombophilia

IntroductionInflammation 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.Subjects and MethodsGenomic 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.ResultsThere 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.ConclusionsOur 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.