Lan Hongtao, Xi Yingbin, Kang Baoxu, Tong Zhoujie, Peng Jie, Zhang Wei, Zhong Ming, Gong Huiping, Wang Zhihao
National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
Department of Geriatric Medicine, Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital of Shandong University, Jinan, China.
J Clin Hypertens (Greenwich). 2025 Jan;27(1):e14959. doi: 10.1111/jch.14959. Epub 2024 Dec 17.
Hypertension is a multifactorial condition influenced by both genetic and environmental factors. Protein disulfide isomerase family A member 3 (PDIA3) is a key endoplasmic reticulum protein which may contribute to increased blood pressure. However, the relationship between PDIA3 polymorphisms and hypertension remain unclear. This study aims to explore the relationship between PDIA3 polymorphisms and hypertension. First, Mendelian randomization (MR) analyses were performed to assess the causal link between PDIA3 and hypertension. Second, key gene polymorphism on PDIA3 was identified using online databases and analyzed with Haploview software. Third, multivariate-adjusted logistic regression analyses were employed to evaluate the associations between PDIA3 rs2788 and hypertension. Finally, stratified analyses were conducted to further assess interactions between PDIA3 rs2788 and antihypertensive medications. MR analyses indicated a causal relationship between PDIA3 and hypertension. The rs2788 gene polymorphism locus on PDIA3 was identified using online databases and Haploview software. Multivariable-adjusted logistic regression analyses revealed that PDIA3 rs2788 was an independent risk for hypertension (OR: 4.603, 95% CI: 2.946-7.194; p < 0.001). Significant interactions were identified between PDIA3 and antihypertensive medications, particularly ACEI/ARB treatments (p = 0.013 for interaction). Similar findings were observed regarding the causal relationship between antihypertensive treatments and hypertension. PDIA3, particularly its rs2788 polymorphisms, may represent a novel biomarker for hypertension. These findings may contribute to the development of targeted screening strategies and personalized treatment approaches for hypertension management.
高血压是一种受遗传和环境因素影响的多因素疾病。蛋白质二硫键异构酶A家族成员3（PDIA3）是一种关键的内质网蛋白，可能与血压升高有关。然而，PDIA3基因多态性与高血压之间的关系仍不清楚。本研究旨在探讨PDIA3基因多态性与高血压之间的关系。首先，进行孟德尔随机化（MR）分析以评估PDIA3与高血压之间的因果关系。其次，使用在线数据库鉴定PDIA3上的关键基因多态性，并使用Haploview软件进行分析。第三，采用多变量调整逻辑回归分析来评估PDIA3 rs2788与高血压之间的关联。最后，进行分层分析以进一步评估PDIA3 rs2788与抗高血压药物之间的相互作用。MR分析表明PDIA3与高血压之间存在因果关系。使用在线数据库和Haploview软件鉴定了PDIA3上的rs2788基因多态性位点。多变量调整逻辑回归分析显示，PDIA3 rs2788是高血压的独立危险因素（OR：4.603，95%CI：2.946 - 7.194；p < 0.001）。在PDIA3与抗高血压药物之间发现了显著的相互作用，特别是ACEI/ARB治疗（交互作用p = 0.013）。关于抗高血压治疗与高血压之间的因果关系也观察到了类似的结果。PDIA3，特别是其rs2788多态性，可能代表高血压的一种新型生物标志物。这些发现可能有助于制定针对性的筛查策略和高血压管理的个性化治疗方法。
