Association between serum alkaline phosphatase levels in late pregnancy and the incidence of venous thromboembolism postpartum: a retrospective cohort study

Li, Qian; Wang, Hongfei; Wang, Huafang; Deng, Jun; Cheng, Zhengwang; Lin, Wenyi; Zhu, Rong; Chen, Shi; Guo, Jinrong; Tang, Liang V.; Hu, Yu

doi:10.1016/j.eclinm.2023.102088

Cited by 4 publications

(2 citation statements)

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“…Research into the enzymatic characteristics of ALP has elucidated that the active site encompasses a serine residue, with a proximate amino acid sequence reminiscent of serine environments [ 22 ]. In healthy adults, serum ALP levels are conventionally found to span from 40 to 150 U/L; deviations from this range are frequently indicative of pathological conditions [ 23 ]. Elevated serum ALP levels, for instance, have been correlated with Multiple Myeloma and osteoblastic bone tumors [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence

Zhu,

Jiang,

et al. 2024

Hum Genomics

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Objective To investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. Methods Genome-wide association studies for OC and levels of enzymes such as Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase, and gamma-glutamyltransferase were analyzed. Univariate and multivariate Mendelian randomization (MR), complemented by the Steiger test, identified enzymes with a potential causal relationship to OC. Single-cell transcriptomics from the GSE130000 dataset pinpointed pivotal cellular clusters, enabling further examination of enzyme-encoding gene expression. Transcription factors (TFs) governing these genes were predicted to construct TF-mRNA networks. Additionally, liver enzyme levels were retrospectively analyzed in healthy individuals and OC patients, alongside the evaluation of correlations with cancer antigen 125 (CA125) and Human Epididymis Protein 4 (HE4). Results A total of 283 single nucleotide polymorphisms (SNPs) and 209 SNPs related to ALP and AST, respectively. Using the inverse-variance weighted method, univariate MR (UVMR) analysis revealed that ALP (P = 0.050, OR = 0.938) and AST (P = 0.017, OR = 0.906) were inversely associated with OC risk, suggesting their roles as protective factors. Multivariate MR (MVMR) confirmed the causal effect of ALP (P = 0.005, OR = 0.938) on OC without reverse causality. Key cellular clusters including T cells, ovarian cells, endothelial cells, macrophages, cancer-associated fibroblasts (CAFs), and epithelial cells were identified, with epithelial cells showing high expression of genes encoding AST and ALP. Notably, TFs such as TCE4 were implicated in the regulation of GOT2 and ALPL genes. OC patient samples exhibited decreased ALP levels in both blood and tumor tissues, with a negative correlation between ALP and CA125 levels observed. Conclusion This study has established a causal link between AST and ALP with OC, identifying them as protective factors. The increased expression of the genes encoding these enzymes in epithelial cells provides a theoretical basis for developing novel disease markers and targeted therapies for OC.

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Section: Discussionmentioning

confidence: 99%

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence

Zhu,

Jiang,

et al. 2024

Hum Genomics

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“… 3 , 4 Our and other studies have identified risk factors for VTE among pregnant women, including characteristics of the mothers (e.g., body mass index (BMI), age, multiple pregnancy), 5 and characteristics of obstetric (e.g., cesarean delivery, preterm delivery, preeclampsia), 5 , 6 , 7 and nutrition status of the mothers (e.g., serum alkaline phosphatase). 8 Abnormal blood pressure (BP) was also found to be related to inflammation and abnormal expression of the adhesion molecules, which may lead to VTE. 9 , 10 BP can be ameliorated with management, appropriate therapy, and/or lifestyle changes.…”

Section: Introductionmentioning

confidence: 99%

Associations of blood pressure in the third trimester and risk of venous thromboembolism postpartum

Li,

Wang,

Wang

et al. 2024

MedComm

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Studies on the associations of blood pressure (BP) and the risk of venous thromboembolism (VTE) had been performed neither among pregnant women nor in Chinese population. This study included participants of pregnant women from a retrospective multicenter cohort, between May 2020 and April 2023. Systolic BP (SBP) and diastolic BP (DBP) of the participants were measured in the third trimester. The incidences of VTE (including deep venous thrombosis and/or pulmonary embolism) at 42 days postpartum were followed. With regards to SBP, pregnant women in the Q1 (≤114 mmHg), Q2 (115–122 mmHg), and Q4 group (≥131 mmHg) had increased risk of VTE than those in Q3 group (123–130 mmHg), with ORs 4.48 [1.69, 11.85], 3.52 [1.30, 9.59], and 3.17 [1.12, 8.99], respectively. Compared with pregnant women with the Q4 of DBP (≥85 mmHg), women of Q1 (≤71 mmHg) were found to have elevated risk of VTE (OR 2.73 [1.25, 5.96]). A one standard deviation decrease of DBP (9 mmHg) was related with 37% elevated risk of VTE (OR 1.37 [1.05, 1.79]). This study demonstrated a U‐shaped association of SBP in the third trimester and VTE postpartum and inverse association of DBP in the third trimester and VTE postpartum.

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Blood cell traits and venous thromboembolism in East Asians: Observational and genetic evidence

Li,

Duo,

Zhang

et al. 2024

iScience

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Association between serum alkaline phosphatase levels in late pregnancy and the incidence of venous thromboembolism postpartum: a retrospective cohort study

Cited by 4 publications

References 30 publications

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence

Associations of blood pressure in the third trimester and risk of venous thromboembolism postpartum

Blood cell traits and venous thromboembolism in East Asians: Observational and genetic evidence

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