性激素结合球蛋白水平与不使用激素避孕药的女性静脉血栓风险没有因果关系。
Sex hormone-binding globulin levels are not causally related to venous thrombosis risk in women not using hormonal contraceptives.
机构信息
Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, the Netherlands.
出版信息
J Thromb Haemost. 2012 Oct;10(10):2061-7. doi: 10.1111/j.1538-7836.2012.04878.x.
BACKGROUND
Oral contraceptive use increases the risk of venous thrombosis as well as sex hormone-binding globulin (SHBG) levels. Furthermore, increased SHBG levels are positively associated with activated protein C (APC) resistance and thrombotic risk in oral contraceptive users.
OBJECTIVES
To determine whether increased SHBG levels are causally related to venous thrombosis in women not using hormonal contraceptives.
METHODS
Premenopausal women were selected from a case-control study on venous thrombosis, the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study (23 patients; 258 controls). Women using hormonal contraceptives were excluded. First, the risk of venous thrombosis with SHBG levels above the normal reference range (70 nm) was determined. Second, because multiple regulatory factors affect SHBG levels and residual confounding may remain, we determined six single-nucleotide polymorphisms (SNPs) in the SHBG gene and assessed the risk of venous thrombosis in a different case-control study, the Leiden Thrombophilia Study (LETS) (20 patients; 74 controls), and in the MEGA study. Finally, the association between SHBG levels and the normalized activated partial thromboplastin time-based APC resistance (an intermediate endpoint for venous thrombosis) was determined.
RESULTS
Elevated SHBG levels (> 70.0 nm) were associated with venous thrombosis (odds ratio 1.92; 95% confidence interval [CI] 0.74-5.00). However, this finding can be explained by residual confounding. Two SNPs in the SHBG gene affected SHBG levels, but not venous thrombosis risk. Furthermore, SHBG levels in controls were not associated with APC resistance (SHBG level, > 70.0 vs. ≤ 70.0 nm: mean difference in normalized APC sensitivity ratio, 0.03; 95% CI -0.05 to 0.10). Exclusion of women with FV Leiden did not materially change these results.
CONCLUSIONS
Increased SHBG levels are not causally related to the risk of venous thrombosis.
背景
口服避孕药的使用会增加静脉血栓形成的风险，以及性激素结合球蛋白（SHBG）水平。此外，SHBG 水平升高与口服避孕药使用者的活化蛋白 C（APC）抵抗和血栓形成风险呈正相关。
目的
确定在不使用激素避孕药的女性中，SHBG 水平升高是否与静脉血栓形成有因果关系。
方法
从静脉血栓形成的病例对照研究，即多环境和遗传因素评估静脉血栓形成危险因素（MEGA）研究（23 例患者；258 例对照）中选择绝经前妇女。排除使用激素避孕药的妇女。首先，确定 SHBG 水平高于正常参考范围（70nm）时静脉血栓形成的风险。其次，由于多个调节因素影响 SHBG 水平，并且可能存在残余混杂，我们在另一个病例对照研究，即莱顿血栓形成倾向研究（LETS）（20 例患者；74 例对照）和 MEGA 研究中确定了 SHBG 基因中的六个单核苷酸多态性（SNP），并评估了静脉血栓形成的风险。最后，确定 SHBG 水平与正常活化部分凝血活酶时间（APTT）基础 APC 抵抗（静脉血栓形成的中间终点）之间的关系。
结果
SHBG 水平升高（>70.0nm）与静脉血栓形成相关（比值比 1.92；95%置信区间[CI]0.74-5.00）。然而，这一发现可以用残余混杂来解释。SHBG 基因中的两个 SNP 影响 SHBG 水平，但不影响静脉血栓形成风险。此外，对照组的 SHBG 水平与 APC 抵抗无关（SHBG 水平，>70.0 vs. ≤70.0nm：正常 APC 敏感性比值的平均差异，0.03；95%CI-0.05 至 0.10）。排除 FV Leiden 女性并不会显著改变这些结果。
结论
SHBG 水平升高与静脉血栓形成风险无因果关系。
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