血清25-羟基维生素D浓度、糖尿病、维生素D受体基因多态性与静脉血栓栓塞事件的关系

Relationship of Serum 25-Hydroxyvitamin D Concentrations, Diabetes, Vitamin D Receptor Gene Polymorphisms and Incident Venous Thromboembolism.

作者信息

Xiang Hao, Zhou Chun, Gan Xiaoqin, Huang Yu, He Panpan, Ye Ziliang, Liu Mengyi, Yang Sisi, Zhang Yanjun, Zhang Yuanyuan, Qin Xianhui

机构信息

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China.

出版信息

Diabetes Metab Res Rev. 2025 Jan;41(1):e70014. doi: 10.1002/dmrr.70014.

DOI:10.1002/dmrr.70014

PMID:39665118

Abstract

AIMS

The association between vitamin D and the risk of venous thromboembolism (VTE) remains inconclusive. We aimed to explore the association of serum 25-hydroxyvitamin D (25OHD) with incident VTE among participants with and without diabetes, and examine the modifying effect of genetic susceptibility of VTE and vitamin D receptor (VDR) gene polymorphisms on this association.

MATERIALS AND METHODS

A total of 378,082 participants free of VTE at baseline from the UK Biobank were included. Serum 25OHD concentrations were measured by the chemiluminescent immunoassay method. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). The genetic risks of VTE were estimated using 297 single nucleotide polymorphisms (SNPs) associated with VTE. The VDR gene polymorphisms included SNPs of rs7975232, rs1544410, rs2228570 and rs731236.

RESULTS

During a median follow-up duration of 12.5 years, 10,645 VTE cases were recorded. Serum 25OHD had a significantly stronger inverse association with incident VTE in participants with diabetes (per SD increment, adjusted HR: 0.87; 95% CI: 0.81-0.93) than in those without diabetes (per SD increment, adjusted HR: 0.97; 95% CI: 0.95-0.99; p-interaction = 0.003). Similar trends were found for incident DVT and PE. Among participants with diabetes, the genetic risk of VTE did not significantly modify the association between serum 25OHD and incident VTE (p-interaction = 0.607). However, a stronger inverse association of serum 25OHD with incident VTE was found in the VDR rs2228570 AA genotype (vs. GG/AG; p-interaction = 0.031).

CONCLUSIONS

Serum 25OHD was inversely associated with the risk of VTE, especially among participants with diabetes, regardless of genetic risks of VTE.

摘要

目的

维生素D与静脉血栓栓塞症（VTE）风险之间的关联尚无定论。我们旨在探讨血清25-羟基维生素D（25OHD）与有或无糖尿病参与者发生VTE之间的关联，并检验VTE遗传易感性和维生素D受体（VDR）基因多态性对这种关联的修饰作用。

材料与方法

纳入了英国生物银行中378,082名基线时无VTE的参与者。采用化学发光免疫分析法测定血清25OHD浓度。主要结局是发生VTE，包括深静脉血栓形成（DVT）和肺栓塞（PE）。使用与VTE相关的297个单核苷酸多态性（SNP）估计VTE的遗传风险。VDR基因多态性包括rs7975232、rs1544410、rs2228570和rs731236的SNP。

结果

在中位随访期12.5年期间，记录了10,645例VTE病例。血清25OHD与糖尿病参与者发生VTE的负相关性（每标准差增加，校正后风险比：0.87；95%置信区间：0.81 - 0.93）显著强于无糖尿病参与者（每标准差增加，校正后风险比：0.97；95%置信区间：0.95 - 0.99；P交互作用 = 0.003）。在发生DVT和PE方面也发现了类似趋势。在糖尿病参与者中，VTE的遗传风险并未显著改变血清25OHD与发生VTE之间的关联（P交互作用 = 0.607）。然而，在VDR rs2228570 AA基因型中发现血清25OHD与发生VTE的负相关性更强（与GG/AG相比；P交互作用 = 0.031）。