Interleukin-10 promoter polymorphism and venous thrombosis

Abstract

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.

Tumor Necrosis Factor Alpha and Interleukin 10 Promoter Polymorphisms in Mexican Patients with Restenosis After Coronary Stenting

“…Several studies suggest that some promoter polymorphisms in the TNF-a and IL-10 genes could regulate the transcription and then define the levels of these cytokines in individuals with different genotypes (Kroeger et al 1997;Wilson et al 1997;Westendorp et al 1997;Crawley et al 1999;Suarez et al 2003;Baseggio et al 2001). TNF-a and IL-10 polymorphisms have been extensively studied in several diseases, including in-stent restenosis (Monraats et al 2007;Koch et al 2003;Oda et al 2007;Bis et al 2008;Settin et al 2007;Rueda et al 2007;Cochery-Nouvellon et al 2006;Crivello et al 2006). The results, however, have been contradictory, with positive and negative associations.…”

“…This cytokine is encoded by a gene located on chromosome 1q32. It presents several polymorphisms (SNPs), three of which (-1082G/A, -819C/T, and -592C/A) have been studied in several diseases, such as atherosclerosis, myocardial infarction, ischemic stroke, rheumatic heart disease, giant cell arteritis, venous thrombosis, and carotid stenosis (Oda et al 2007;Bis et al 2008;Settin et al 2007;Rueda et al 2007;Cochery-Nouvellon et al 2006;Crivello et al 2006). The level of expression of IL-10 is highly variable; 75% of this variability is due to genotypes of these polymorphisms (Westendorp et al 1997;Crawley et al 1999).…”

Biomarkers for the diagnosis of deep vein thrombosis

“…IL-10, a major immunoregulatory and anti-inflammatory cytokine has been linked to DVT. Animal models have demonstrated that IL-10 modulates the development of DVT [31]. Additionally, a human case--control study evaluated IL-10 polymorphisms as a risk factor for venous thrombosis; the authors demonstrated that IL-10 G13 and G10 alleles were independent risk factors for venous thrombosis and that the IL-10 G10 allele was more frequent in recurrent disease, suggesting that it may be an independent risk factor for recurrent disease.…”

Interleukin 10 Gene Promoter Polymorphisms in Women with Pregnancy Loss: Preferential Association with Embryonic Wastage1

“…Positive controls and IL10 promoter polymorphism alleles were determined by PCR. The PCR conditions were previously described by Cochery-Nouvellon et al [25]. Terminology for microsatellites and SNP alleles is based on the international nomenclature (http://www.hgvs.org/).…”

“…Because IL10 down-regulates TF expression [24], we hypothized that this cytokine might have a physiological antithrombotic effect in the form of a defect in IL10 production, inducing placental vascular insufficiency and pregnancy failure. We previously showed that the risk of venous thrombosis [25] is modulated by the IL10 promoter polymorphisms IL10 X78437.2:g.8134CA [26] and IL10 X78437.2:g.8134CA [23].…”