Selectin haplotypes and the risk of venous thrombosis: influence of linkage disequilibrium with the factor V Leiden mutation
Selectin haplotypes and the risk of venous thrombosis: influence of linkage disequilibrium with the factor V Leiden mutation
复制标题
DOI：
10.1111/j.1538-7836.2007.02879.x
复制
发表时间：
2008-03-01
影响因子：
10.4
通讯作者：
Bertina, R. M.
中科院分区：
文献类型：
--
作者：
De Willige, S. Uitte;De Visser, M. C. H.;Bertina, R. M.
背景：选择素（E-、L-和P-选择素）及其最重要的反受体P-选择素糖蛋白配体（SELPLG）促进炎症部位血小板、白细胞和内皮细胞的相互作用。选择素多态性/单倍型与心血管疾病相关。目的：我们研究了这四个基因的单倍型 (H) 与深静脉血栓 (DVT) 风险之间的关联。我们还探讨了连锁不平衡 (LD) 与附近的因子 V Leiden 突变 (FVL) 的影响。此外，还研究了 SELPLG 多态性和选择素多态性之间的相互作用。患者/方法：莱顿血栓形成倾向研究 (LETS) 受试者通过 TaqMan 或 PCR-RFLP 进行 24 种多态性基因分型，检测四个区块中的所有常见单倍型。 P-选择素在重组热点的上游 (SELPup) 和下游 (SELPdown) 两个模块中进行分析。结果：在 E-和 L-选择素中，没有一个单倍型与 DVT 风险相关。在 SELPup 中，H2 携带者的风险增加了 1.3 倍（95% CI，1.0-1.7），而 H4 携带者的风险降低了 1.4 倍（95% CI，0.5-1.0）。在 SELPdown 中，H2 携带者的风险增加 1.3 倍（95% CI，1.0-1.7）。由于 LD 伴有 FVL，我们随后排除了所有 FVL 携带者，所有风险都消失了。逻辑回归模型内的相互调整导致 SELP 单倍型的风险消失，而 FVL 风险仍然存在。结论：用FVL调整LD后，没有一个选择素单倍型与DVT风险相关，表明选择素单倍型风险的增加反映了FVL对血栓形成风险的影响。
Background: Selectins (E-, L- and P-selectin) and their most important counter-receptor P-selectin glycoprotein ligand (SELPLG) facilitate the interaction of platelets, leukocytes and endothelial cells at inflammatory sites. Selectin polymorphisms/haplotypes have been associated with cardiovascular disease. Objectives: We investigated the association between haplotypes (H) of these four genes and deep venous thrombosis (DVT) risk. We additionally explored the effect of linkage disequilibrium (LD) with the nearby Factor V Leiden mutation (FVL). Furthermore, interactions between SELPLG polymorphisms and selectin polymorphisms were investigated. Patients/methods: Leiden Thrombophilia Study (LETS) subjects were genotyped for 24 polymorphisms by TaqMan or PCR-RFLP, detecting all common haplotypes in four blocks. P-selectin was analyzed in two blocks, upstream (SELPup) and downstream (SELPdown) of the recombination hotspot. Results: In E- and L-selectin, none of the haplotypes was associated with DVT risk. In SELPup, H2-carriers had a 1.3-fold increased risk (95% CI, 1.0-1.7), whereas H4-carriers had a 1.4-fold decreased risk (95% CI, 0.5-1.0). In SELPdown, H2-carriers had a 1.3-fold increased risk (95% CI, 1.0-1.7). Because of LD with FVL, we subsequently excluded all FVL-carriers and all risks disappeared. Mutual adjustment within a logistic regression model resulted in disappearance of the risks for the SELP haplotypes, whereas FVL risk remained. Conclusions: After adjustment for LD with FVL, none of the selectin haplotypes was associated with DVT risk, showing that the increased risks of the selectin haplotypes were a reflection of the effect of FVL on thrombosis risk.