Genetic variants associated with deep vein thrombosis: the F11 locus
Genetic variants associated with deep vein thrombosis: the F11 locus
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DOI：
10.1111/j.1538-7836.2009.03544.x
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发表时间：
2009-11-01
影响因子：
10.4
通讯作者：
Rosendaal, F. R.
中科院分区：
文献类型：
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作者：
Li, Y.;Bezemer, I. D.;Rosendaal, F. R.
背景：最近的研究发现，深静脉血栓 (DVT) 与 4q35.2 位点中的单核苷酸多态性 (SNP) 之间存在关联，该位点包含编码因子 XI (F11)、细胞色素 P450 家族成员 (CYP4V2) 和前激肽释放酶 (KLKB1) 的基因。 目的：我们研究了该位点中哪些常见 SNP 与 DVT 独立相关。方法：研究人群是莱顿血栓形成倾向研究 (LETS)（443 例 DVT 病例和 453 例对照）以及静脉血栓形成危险因素的多重环境和遗传评估（MEGA 研究）（2712 例 DVT 病例和 4634 例对照）。我们使用逻辑回归评估了 DVT 与 200 kb 区域中的 103 个 SNP 之间的关联。结果：我们发现两个 SNP（F11 中的 rs2289252 和 rs2036914）与 DVT 独立相关。调整年龄、性别和其他 SNP 后，这两个 SNP 的比值比（风险与非风险纯合子）对于 rs2289252 为 1.49（95% CI，1.25-1.76），对于 rs2036914 为 1.33（95% CI，1.11-1.59）。我们发现 rs2289252 也与 FXI 水平相关，正如之前报道的 rs2036914 一样；在对 FXI 水平进行调整后，这两个 SNP 仍然与 DVT 相关，但风险估计有所减弱。结论：F11 中的两个 SNP（rs2289252 和 rs2036914）似乎独立地增加了 DVT 的风险，这一贡献至少部分是通过与 FXI 水平的关联来解释的。
Background: Recent studies have found associations between deep vein thrombosis (DVT) and single nucleotide polymorphisms (SNPs) in a 4q35.2 locus that contains genes encoding factor XI (F11), a cytochrome P450 family member (CYP4V2), and prekallikrein (KLKB1).Objective: We investigated which of the common SNPs in this locus are independently associated with DVT.Methods: The study populations were the Leiden Thrombophilia Study (LETS) (443 DVT cases and 453 controls) and the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study) (2712 DVT cases and 4634 controls). We assessed the association between DVT and 103 SNPs in a 200 kb region using logistic regression.Results: We found that two SNPs (rs2289252 and rs2036914 in F11) were independently associated with DVT. After adjusting for age, sex, and the other SNP, the odds ratios (risk vs. non-risk homozygotes) of these two SNPs were 1.49 for rs2289252 (95% CI, 1.25-1.76) and 1.33 for rs2036914 (95% CI, 1.11-1.59). We found that rs2289252 was also associated with FXI levels, as has been previously reported for rs2036914; these two SNPs remained associated with DVT with somewhat attenuated risk estimates after adjustment for FXI levels.Conclusion: Two SNPs, rs2289252 and rs2036914 in F11, appear to independently contribute to the risk of DVT, a contribution that is explained at least in part by an association with FXI levels.