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性激素结合球蛋白与妊娠期高血压和子痫前期的因果关系:两样本孟德尔随机化研究。

Causal association of sex hormone-binding globulin on gestational hypertension and pre-eclampsia: a two-sample Mendelian randomization study.

机构信息

The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China.

Department of Cardiology, The First Hospital of Putian City, Putian, Fujian, China.

出版信息

J Matern Fetal Neonatal Med. 2024 Dec;37(1):2389979. doi: 10.1080/14767058.2024.2389979. Epub 2024 Sep 16.

Abstract

OBJECTIVES

Pre-eclampsia (PE) and gestational hypertension (GH) are two different categories of hypertensive disorders of pregnancy. Given earlier observational research, the relationship between sex hormone-binding globulin (SHBG) and a higher risk of GH/PE is still up for dispute. Hence, the present investigation aimed to examine the possible link between SHBG and the likelihood of GH/PE.

METHODS

As a first stage, single nucleotide polymorphisms from summary-level genome-wide association studies were tightly screened using quality-control techniques. Afterward, we utilized a two-sample Mendelian randomization (MR) study to examine the causal impact of SHBG on the likelihood of GH/PE. There was no indication of a relationship between blood SHBG level ( = 214,989) and GH/PE (1864 cases and 461,069 controls) in the initial study. Consensus results were obtained from the replicated analysis, which utilized MR estimates based on serum SHBG level( = 214,989) for GH (4255 cases and 114,735 controls).

RESULTS

The findings did not indicate any proof of a cause-and-effect connection between SHBG and the likelihood of GH/PE (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.999 - 1.00,  = .34). Replicate analysis also revealed similar patterns (OR = 0.92, 95%CI = 0.82-1.05,  = .21). The above findings were demonstrated to have a strong level of robustness.

CONCLUSIONS

The findings of this research did not offer definitive proof to endorse the idea that SHBG has a direct causal impact on the likelihood of GH/PE, which goes against numerous widely accepted observational studies. To ascertain the potential processes behind the relationships seen in observational studies, more investigation is needed.

摘要

目的

子痫前期(PE)和妊娠期高血压(GH)是妊娠高血压疾病的两种不同类别。鉴于早期的观察性研究,性激素结合球蛋白(SHBG)与 GH/PE 风险增加之间的关系仍存在争议。因此,本研究旨在探讨 SHBG 与 GH/PE 可能性之间的可能联系。

方法

作为第一阶段,使用质量控制技术对汇总水平全基因组关联研究的单核苷酸多态性进行了严格筛选。然后,我们利用两样本孟德尔随机化(MR)研究来检验 SHBG 对 GH/PE 可能性的因果影响。在初始研究中,血液 SHBG 水平(=214989)与 GH/PE(1864 例和 461069 例对照)之间没有关系。从基于血清 SHBG 水平的 GH 的复制分析中获得了共识结果(=214989,4255 例和 114735 例对照)。

结果

研究结果没有表明 SHBG 与 GH/PE 可能性之间存在因果关系的任何证据(比值比[OR] =0.99,95%置信区间[CI] =0.999-1.00, =0.34)。复制分析也显示出类似的模式(OR=0.92,95%CI=0.82-1.05, =0.21)。上述发现具有很强的稳健性。

结论

本研究的结果没有提供明确的证据支持 SHBG 对 GH/PE 可能性有直接因果影响的观点,这与许多广泛接受的观察性研究背道而驰。为了确定观察性研究中观察到的关系背后的潜在过程,需要进一步研究。

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