Implications of lipoprotein (a) [Lp(a)] gene polymorphic sequence variations and its protein expression in venous thromboembolism (VTE)

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-07-18 DOI:10.1016/j.bbrep.2025.102152

Karan Happa , Arshad A. Pandith , Umar H. Khan , Shayaq Ul Abeer Rasool , Aabid M. Koul , Qurat Ul Ain , Mir Uzair ul Haq , Usma Manzoor , Adil Lateef , Rafi A. Jan

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引用次数: 0

Abstract

Background

Venous thromboembolism (VTE) is a significant global health concern, with an annual incidence of approximately 1–2 per 1000 individuals. VTE is a major cause of morbidity and mortality worldwide, leading to substantial healthcare costs due to hospitalizations, long-term anticoagulation therapy, recurrent thrombotic events and the need for lifelong clinical management. The burden of VTE is particularly pronounced in aging populations, with incidence rates increasing exponentially after the age of 50. Despite its significant impact, the genetic underpinnings of VTE remain incompletely understood. This study investigates the association of Lp(a) gene polymorphisms (93C > T and 121G > A) and Lp(a) expression with VTE risk.

Methods

A case-control study was conducted, enrolling 101 VTE cases and 110 healthy, age- and gender-matched controls. Genotyping was performed using PCR-RFLP, and serum Lp(a) levels were quantified using ELISA. Genotype distribution and their association with VTE risk was determined by statistical analyses.

Results

The +121 G > A polymorphism exhibited a significant protective effect, with the GA genotype more prevalent in controls than cases (OR = 0.41, 95 % CI = 0.23–0.73, p = 0.002). Additionally, the combined GA + AA genotypes were significantly associated with a lower VTE risk (OR = 0.44, p = 0.003). Serum Lp(a) levels were elevated in VTE cases (mean VTE 36.41 mg/dl) compared to controls (mean 32.00 mg/dl, p < 0.84). Notably, this difference was most pronounced in the 30–70 mg/dl subgroup (p < 0.01). D-Dimer was significantly elevated in VTE (p < 0.001) and GA + AA genotype was significantly more frequent in control subjects with D-Dimer levels <500 ng/ml (OR = 0.23, 95 % CI = 0.05–0.95, p = 0.04. LP (a)+121 G > A variant genotype was significantly higher in controls for males, smokers and BMI ≤25 than VTE cases (p < 0.05). No significant difference was found in LP(a) +93C > T with VTE risk.

Conclusion

Our study concludes the inverse role of Lp(a) polymorphic variation +121 G > A in the pathogenesis of VTE. +93C > T variant and serum lipoprotein (a) levels did not increase the risk of pathogenesis of VTE. However, gender specific impact of LP(a) on VTE is plausible.

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脂蛋白(a) [Lp(a)]基因多态性序列变异及其蛋白表达在静脉血栓栓塞（VTE）中的意义

静脉血栓栓塞（VTE）是一个重要的全球健康问题，年发病率约为每1000人1-2例。静脉血栓栓塞是世界范围内发病率和死亡率的主要原因，由于住院治疗、长期抗凝治疗、复发性血栓事件和终身临床管理的需要，导致了大量的医疗费用。静脉血栓栓塞的负担在老年人群中尤为明显，50岁以后发病率呈指数增长。尽管静脉血栓栓塞有重大影响，但其遗传基础仍不完全清楚。本研究探讨了Lp(a)基因多态性(93C >；T和121G >；A)和Lp(A)表达与静脉血栓栓塞风险有关。方法采用病例对照研究，纳入101例静脉血栓栓塞病例和110例年龄、性别匹配的健康对照组。采用PCR-RFLP法进行基因分型，ELISA法测定血清Lp(a)水平。通过统计分析确定基因型分布及其与静脉血栓栓塞风险的关系。结果+121 G >；多态性显示出显著的保护作用，GA基因型在对照组中比在病例中更普遍（OR = 0.41, 95% CI = 0.23-0.73, p = 0.002）。此外，GA + AA联合基因型与较低的静脉血栓栓塞风险显著相关（OR = 0.44, p = 0.003）。静脉血栓栓塞患者血清Lp(a)水平（平均VTE 36.41 mg/dl）高于对照组(平均32.00 mg/dl, p <；0.84)。值得注意的是，这种差异在30-70 mg/dl亚组中最为明显(p <；0.01)。d -二聚体在VTE中显著升高(p <；0.001)和GA + AA基因型在d -二聚体水平为500 ng/ml的对照组中更为常见（OR = 0.23, 95% CI = 0.05-0.95, p = 0.04）。LP (a)+121 G >；在男性、吸烟者和BMI≤25的对照组中，变异基因型明显高于静脉血栓栓塞病例(p <；0.05)。LP(a) +93C >无显著性差异；有静脉血栓栓塞风险。结论Lp(a)多态性变异+121 G >；静脉血栓栓塞的发病机制。+ 93 c比;T变异和血清脂蛋白(a)水平没有增加静脉血栓栓塞发病的风险。然而，LP(a)对静脉血栓栓塞的性别特异性影响是可信的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.