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Thromb Haemost 2006; 96(01): 24-28
DOI: 10.1160/TH06-01-0027
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Interleukin-10 promoter polymorphism and venous thrombosis

A case-control study
Eva Cochery-Nouvellon
1   Laboratoire Central d’hématologie
3   Unité UPRES EA3796 IFR53, Faculté de Médecine et de Pharmacie, Université de Reims Champagne-Ardenne, France
,
Fabien Vitry
2   Unité d’aide méthodologique, CHU Robert Debré
,
Pascale Cornillet-Lefebvre
1   Laboratoire Central d’hématologie
3   Unité UPRES EA3796 IFR53, Faculté de Médecine et de Pharmacie, Université de Reims Champagne-Ardenne, France
,
Nathalie Hezard
1   Laboratoire Central d’hématologie
,
Lucile Gillot
1   Laboratoire Central d’hématologie
,
Philippe Nguyen
1   Laboratoire Central d’hématologie
3   Unité UPRES EA3796 IFR53, Faculté de Médecine et de Pharmacie, Université de Reims Champagne-Ardenne, France
› Author Affiliations
Further Information

Publication History

Received 17 January 2006

Accepted after resubmission 14 May 2006

Publication Date:
29 November 2017 (online)

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Summary

The human interleukin-10 promoter gene is highly polymorphic. IL-10 polymorphisms have been associated with various autoimmune and lymphoproliferative disorders. Although IL-10 has been shown to modulate thrombin generation in several experimental models, it is not known whether IL-10 polymorphisms could be a risk factor for venous thrombosis. We therefore conducted a case-control study comparing 74 consecutive patients who experienced at least one episode of documented venous thromboembolic event and 100 healthy controls. All subjects were Caucasians. Five polymorphisms of the IL-10 promoter gene were studied: two highly polymorphic dinucleotide repeats, IL-10 R and IL-10G, and three single nucleotide polymorphisms at position −1082, −819 and −592. Factor VG1691C Leiden mutation was systematically determined. Multivariate logistic regression analysis showed that IL-10 G13 and G10 alleles are independent risk factors for venous thrombosis (Odds ratio:OR = 3.33, p = 0.003 and OR = 2.83, p = 0.03, respectively). Furthermore, IL-10 G10 allele is more frequent in recurrent disease.

Keywords

Deep vein thrombosis - interleukin-10 - factor V Leiden - hereditary thrombosis risk factor
 

  • References

  • 1 Bertina RM, Koeleman BP, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
    CrossrefPubMedGoogle Scholar
  • 2 Fiorentino DF, Zlotnik A, Mosmann TR. et al. IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815-22.
    PubMedGoogle Scholar
  • 3 De Waal RMalefyt, Abrams J. et al. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209-20.
    CrossrefPubMedGoogle Scholar
  • 4 Eskdale J, Gallagher G. A polymorphic dinucleotide repeat in the human IL-10 promoter. Immunogenetics 1995; 42: 444-5.
    PubMedGoogle Scholar
  • 5 Eskdale J, Kube D, Gallagher G. A second polymorphic dinucleotide repeat in the 5’ flanking region of the human IL10 gene. Immunogenetics 1996; 45: 82-3.
    CrossrefPubMedGoogle Scholar
  • 6 Turner DM, Williams DM, Sankaran D. et al. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1-8.
    CrossrefPubMedGoogle Scholar
  • 7 Khatri VP, Caligiuri MA. A review of the association between interleukin-10 and human B-cell malignancies. Cancer Immunol Immunother 1998; 46: 239-44.
    CrossrefPubMedGoogle Scholar
  • 8 Kube D, Platzer C, von Knethen A. et al. Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt’s lymphoma cell lines. Cytokine 1995; 07: 1-7.
    CrossrefPubMedGoogle Scholar
  • 9 Beebe AM, Cua DJ, de Waal RMalefyt. The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev 2002; 13: 403-12.
    CrossrefPubMedGoogle Scholar
  • 10 Eskdale J, McNicholl J, Wordsworth P. et al. Interleukin-10 microsatellite polymorphisms and IL-10 locus alleles in rheumatoid arthritis susceptibility. Lancet 1998; 352: 1282-3.
    CrossrefPubMedGoogle Scholar
  • 11 Downing LJ, Strieter RM, Kadell A. et al. IL-10 regulates thrombus-induced vein wall inflammation and thrombosis. J Immunol 1998; 161: 1471-6.
    PubMedGoogle Scholar
  • 12 Henke PK, DeBrunye LA, Strieter RM. et al. Viral IL-10 gene transfer decreases inflammation and cell adhesion molecule expression in a rat model of venous thrombosis. J Immunol 2000; 164: 2131-41.
    CrossrefPubMedGoogle Scholar
  • 13 Wakefield TW, Strieter RM, Wilke CA. et al. Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 258-68.
    CrossrefPubMedGoogle Scholar
  • 14 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
    CrossrefPubMedGoogle Scholar
  • 15 Hezard N, Cornillet-lefebvre P, Droulle C. et al. Factor V Leiden: detection in whole blood by ASA PCR using an additional mismatch in antepenultimate position. Thromb Res 1997; 88: 59-66.
    CrossrefPubMedGoogle Scholar
  • 16 Hezard N, Cornillet-lefebvre P, Gillot L. et al. Multiplex ASA PCR for simultaneous determination of factor V Leiden gene, G-->A 20210 prothrombin gene and C-->T 677 MTHFR gene mutations. Thromb Haemost 1998; 79: 1054-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Ridker PM, Miletich JP, Hennekens CH. et al. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 1997; 277: 1305-7.
    CrossrefPubMedGoogle Scholar
  • 18 Font J, Garcia-Carrasco M, Ramos-Casals M. et al. The role of interleukin-10 promoter polymorphisms in the clinical expression of primary Sjogren’s syndrome. Rheumatology 2002; 41: 1025-30.
    CrossrefPubMedGoogle Scholar
  • 19 Crawley E, Kon S, Woo P. Hereditary predisposition to low interleukin-10 production in children with extended oligoarticular juvenile idiopathic arthritis. Rheumatology 2001; 40: 574-8.
    CrossrefPubMedGoogle Scholar
  • 20 Hobbs K, Negri J, Klinnert M. et al. Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med 1998; 158: 1958-62.
    CrossrefPubMedGoogle Scholar
  • 21 Kitawaki J, Obayashi H, Ohta M. et al. Genetic contribution of the interleukin-10 promoter polymorphism in endometriosis susceptibility. Am J Reprod Immunol 2002; 47: 12-8.
    CrossrefPubMedGoogle Scholar
  • 22 Anaya JM, Correa PA, Herrera M. et al. Interleukin 10 (IL-10) influences autoimmune response in primary Sjogren’s syndrome and is linked to IL-10 gene polymorphism. J Rheumatol 2002; 29: 1874-6.
    PubMedGoogle Scholar
  • 23 Tegoshi H, Hasegawa G, Obayashi H. et al. Polymorphisms of interferon-gamma gene CA-repeat and interleukin-10 promoter region (-592A/C) in Japanese type I diabetes. Hum Immunol 2002; 63: 121-8.
    CrossrefPubMedGoogle Scholar
  • 24 Santos AR, Suffys PN, Vanderborght PR. et al. Role of tumor necrosis factor-alpha and interleukin-10 promoter gene polymorphisms in leprosy. J Infect Dis 2002; 186: 1687-91.
    CrossrefPubMedGoogle Scholar
  • 25 Martinez-Escribano JA, Moya-Quiles MR, Muro M. et al. Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients. Melanoma Res 2002; 12: 465-9.
    CrossrefPubMedGoogle Scholar
  • 26 Gibson AW, Edberg JC, Wu J. et al. Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 2001; 166: 3915-22.
    CrossrefPubMedGoogle Scholar
  • 27 Eskdale J, Wordsworth P, Bowman S. et al. Association between polymophisms at the human IL-10 locus and systemic lupus erythematosus. Tissue Antigens 1997; 49: 635-9.
    CrossrefPubMedGoogle Scholar
  • 28 Asadullah K, Eskdale J, Wiese A. et al. Interleukin-10 promoter polymorphism in psoriasis. J Invest Dermatol 2001; 116: 975-8.
    CrossrefPubMedGoogle Scholar
  • 29 Goedecke V, Crane AM, Jaakkola E. et al. Interleukin 10 polymorphisms in ankylosing spondylitis. Genes Immun 2003; 04: 74-6.
    CrossrefPubMedGoogle Scholar
  • 30 Kaluza W, Leirisalo-Repo M, Marker-Hermann E. et al. IL 10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients. Arthritis Rheum 2001; 44: 1209-14.
    CrossrefPubMedGoogle Scholar
  • 31 Martinez ADoncel, Rubio A, Arroyo R. et al. Interleukin-10 polymorphisms in Spanish multiple sclerosis patients. J Neuroimmunol 2002; 131: 168-72.
    CrossrefPubMedGoogle Scholar
  • 32 Huang DR, Zhou YH, Xia SQ. et al. Markers in the promoter region of interleukin-10 (IL-10) gene in myasthenia gravis: implication of diverses effects of Il-10 in the pathogenesis of the disease. J Neuroimmunol 1999; 94: 82-7.
    CrossrefPubMedGoogle Scholar
  • 33 Van der Linde K, Boor PP, Sandkuijl LA. et al. A Gly 15 Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease. Scand J Gastroenterol 2003; 38: 611-7.
    CrossrefPubMedGoogle Scholar
  • 34 Llorente L, Zou W, Richaud-Patin Y. et al. I vivo production of interleukin-10 by non-T-cells in rheumatoid arthritis, Sjögren’s syndrome and systemic lupus erythematosus. Arthritis Rheum 1994; 37: 1647-55.
    CrossrefPubMedGoogle Scholar
  • 35 Hensen P, Asadullah K, Windemuth C. et al. Interleukin-10 promoter IL10.G and familial early onset psoriasis. Br J Dermatol 2003; 149: 381-5.
    CrossrefPubMedGoogle Scholar
  • 36 Kube D, Schmidt D, Mörmann M. et al. Semiautomated and simultaneous analysis of the interleukin-10 microsatellites IL-G and IL-R by fluorescence-based polymerase chain reaction reveals significant differences in allele distributions between Caucasians (Germany) and Africans (Gabon). Eur Cytokine Netw 2001; 12: 537-44.
    PubMedGoogle Scholar
  • 37 Eskdale J, Kube D, Tesch H. et al. Mapping of the human IL10 gene and further characterization of the 5’ flanking sequence. Immunogenetics 1997; 46: 120-8.
    CrossrefPubMedGoogle Scholar