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Objective— It has been suggested that the overall effect of the major proinflammatory cytokine interleukin-1 (IL-1) on coagulation and fibrinolysis is prothrombotic. The aim of this study was to investigate whether common variations inIL1B ,IL1RN ,IL1R1 , andIL1R2 influence the risk of venous thrombosis.Methods and Results— In a case–control study on the causes of deep venous thrombosis, the Leiden Thrombophilia Study (LETS), we genotyped 18 single nucleotide polymorphisms (SNPs) inIL1B ,IL1RN ,IL1R1 , andIL1R2 , enabling us to tag a total of 25 haplotype groups. Overall testing of the haplotype frequency distribution in patients and controls indicated that a recessive effect was present inIL1RN (P =0.031). Subsequently the risk of venous thrombosis was calculated for each haplotype ofIL1RN . Increased thrombotic risk was found for homozygous carriers of haplotype 5 (H5, tagged by SNP 13888T/G, rs2232354) ofIL1RN (Odds ratio=3.9; 95% confidence interval: 1.6 to 9.7;P =0.002). No risk was associated with haplotype 3 ofIL1RN , which contains the frequently examined allele 2 variant of the intron 2 VNTR.Conclusions— We found thatIL1RN –H5H5 carriership increases the risk of venous thrombosis.

Haplotypes ofIL1B,IL1RN,IL1R1, andIL1R2and the Risk of Venous Thrombosis