Zee Robert Y L, Glynn Robert J, Cheng Suzanne, Steiner Lori, Rose Lynda, Ridker Paul M
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Circ Cardiovasc Genet. 2009 Feb;2(1):57-62. doi: 10.1161/CIRCGENETICS.108.801969. Epub 2009 Jan 23.
Although pathways associated with hemostasis and thrombosis are well documented to have an impact on venous thromboembolism (VTE), whether the inflammatory cascade also influences VTE risk is uncertain.
We evaluated 51 polymorphisms from 32 inflammation-related genes (and an additional 19 polymorphisms from 15 thrombosis-related genes) as potential determinants of VTE in a prospective cohort of 22 413 white women followed over a 10-year period. Hazard ratios (HRs) for incident VTE according to the different genotypes were assessed by Cox proportional-hazards models. The false discovery rate (FDR) was used for correction for multiple testing with a 0.20 cut point. During follow-up, 158 idiopathic and 180 secondary VTE events occurred. As anticipated, factor V Leiden (HR, 3.22; 95% CI, 1.92 to 5.40; P<0.0001; FDR=0.004) and the prothrombin mutation (HR, 2.57; 95% CI, 1.64 to 4.02; P<0.0001; FDR=0.004) were both strongly associated with incident idiopathic VTE, as was the rs6046 polymorphism in the factor VII gene (HR, 0.54; 95% CI, 0.35 to 0.86; P=0.008; FDR, 0.12). With regard to polymorphism in the inflammatory genes, variation at rs1143634 in the IL-1beta gene was associated with a reduced risk of idiopathic VTE (HR, 0.59; 95% CI, 0.44 to 0.80; P=0.0007; FDR=0.02), whereas variation at rs1800872 in the IL-10 gene was associated with increased risk (HR, 1.42; 95% CI, 1.12 to 1.80; P=0.004; FDR=0.07). By contrast, no significant associations were found for secondary VTE events.
In addition to previously reported polymorphisms associated with hemostasis and thrombosis, these prospective cohort data suggest that genetic variation in IL-1 beta and IL-10 genes may also influence the risk of idiopathic VTE.
尽管与止血和血栓形成相关的通路对静脉血栓栓塞（VTE）的影响已有充分记录，但炎症级联反应是否也会影响VTE风险尚不确定。
我们在一个为期10年的前瞻性队列中，评估了来自32个炎症相关基因的51个多态性（以及来自15个血栓形成相关基因的另外19个多态性），作为VTE的潜在决定因素，该队列包括22413名白人女性。根据不同基因型的VTE发病风险比（HRs）通过Cox比例风险模型进行评估。错误发现率（FDR）用于多重检验校正，临界值为0.20。在随访期间，发生了158例特发性VTE事件和180例继发性VTE事件。正如预期的那样，因子V Leiden（HR，3.22；95%CI，1.92至5.40；P<0.0001；FDR=0.004）和凝血酶原突变（HR，2.57；95%CI，1.64至4.02；P<0.0001；FDR=0.004）均与特发性VTE发病密切相关，因子VII基因中的rs6046多态性也是如此（HR，0.54；95%CI，0.35至0.86；P=0.008；FDR，0.12）。关于炎症基因的多态性，IL-1β基因中rs1143634的变异与特发性VTE风险降低相关（HR，0.59；95%CI，0.44至0.80；P=0.0007；FDR=0.02），而IL-10基因中rs1800872的变异与风险增加相关（HR，1.42；95%CI，1.12至1.80；P=0.004；FDR=0.07）。相比之下，继发性VTE事件未发现显著关联。
除了先前报道的与止血和血栓形成相关的多态性外，这些前瞻性队列数据表明，IL-1β和IL-10基因的遗传变异也可能影响特发性VTE的风险。
