Single nucleotide polymorphisms in inflammation-related genes are associated with venous thromboembolism

Abstract 

Background

Various genetic risk factors are known to increase the risk of venous thromboembolism (VTE). Increasing evidence suggests a “cross-talk” between the coagulation and inflammatory cascade. Therefore, polymorphisms in genes involved in inflammation may influence susceptibility towards VTE. The aim of the study was to investigate the role of single nucleotide polymorphisms (SNPs) in inflammation genes for susceptibility towards VTE.

Methods

The study group consisted of 108 (47 men and 61 women) Dutch patients with documented VTE and 325 healthy controls from the same geographical area (117 men and 208 women). Odds ratios (OR) and 95% confidence intervals (95% CI) for VTE separately and if indicated by gender were calculated to assess whether genotype and allele frequency were associated with thrombosis.

Results

Heterozygosity for SNP −899C/T of the interleukin 1-alpha gene (IL1A −899C/T) was under-represented in VTE patients compared to the control group (OR=0.51, 95% CI 0.32–0.82). The IL6 −174 CC genotype was more frequent in male patients with VTE compared to male controls (OR=4.06, 95% CI 1.43–11.5). Female patients carried significantly more IL13 (intron3) TT genotype (OR=5.60, 95% CI 1.94–18.5) compared to female controls. The allelic frequency of IL4 −589 T allele was significantly increased in female patients (OR=1.72, 95% CI 1.05–2.81) in contrast to men where no differences were observed.

Conclusion

Four SNPs in inflammatory-related genes of IL1A, IL4, IL6, and IL13 may be associated with VTE. These results need to be confirmed in independent groups with larger number of patients.

Keywords: Gene polymorphisms, Inflammation, Venous thromboembolism, VTE