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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1486.)
© 2007 American Heart Association, Inc.

Thrombosis

Haplotypes of IL1B, IL1RN, IL1R1, and IL1R2 and the Risk of Venous Thrombosis

Rick van Minkelen; Marieke C.H. de Visser; Jeanine J. Houwing-Duistermaat; Hans L. Vos; Rogier M. Bertina; Frits R. Rosendaal

From the Hemostasis and Thrombosis Research Center, Department of Hematology (R.v.M., M.C.H.d.V., H.L.V., R.M.B., F.R.R.), the Department of Medical Statistics and Bioinformatics (J.J.H.-D.), and the Department of Clinical Epidemiology (F.R.R.), Leiden University Medical Center, Leiden, The Netherlands.

Correspondence to Frits R. Rosendaal, Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E-mail f.r.rosendaal{at}lumc.nl

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 in IL1B, IL1RN, IL1R1, and IL1R2 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) in IL1B, IL1RN, IL1R1, and IL1R2, 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 in IL1RN (P=0.031). Subsequently the risk of venous thrombosis was calculated for each haplotype of IL1RN. Increased thrombotic risk was found for homozygous carriers of haplotype 5 (H5, tagged by SNP 13888T/G, rs2232354) of IL1RN (Odds ratio=3.9; 95% confidence interval: 1.6 to 9.7; P=0.002). No risk was associated with haplotype 3 of IL1RN, which contains the frequently examined allele 2 variant of the intron 2 VNTR.

Conclusions— We found that IL1RN–H5H5 carriership increases the risk of venous thrombosis.

The effect of variations in IL1B, IL1RN, IL1R1, and IL1R2 on venous thrombosis risk was investigated by a haplotype-based approach. Homozygous carriership of haplotype 5 of IL1RN (tagged by SNP 13888T/G, rs2232354) was associated with an increased risk of venous thrombosis (OR=3.9; 95% CI:1.6 to 9.7; P=0.002).

Key Words: venous thrombosis • inflammation • IL-1 • haplotypes • risk factors