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内脏脂肪素与中轴型脊柱关节炎的动脉粥样硬化疾病及心血管风险:一项遗传学和血清学研究

Vaspin in atherosclerotic disease and cardiovascular risk in axial spondyloarthritis: a genetic and serological study.

作者信息

Rueda-Gotor Javier, López-Mejías Raquel, Remuzgo-Martínez Sara, Pulito-Cueto Verónica, Corrales Alfonso, Lera-Gómez Leticia, Portilla Virginia, González-Mazón Íñigo, Blanco Ricardo, Expósito Rosa, Mata Cristina, Llorca Javier, Hernández-Hernández Vanesa, Rodríguez-Lozano Carlos, Barbarroja Nuria, Castro Rafaela Ortega, Vicente Esther, Fernández-Carballido Cristina, Martínez-Vidal María Paz, Castro-Corredor David, Anino-Fernández Joaquín, Peiteado Diana, Plasencia-Rodríguez Chamaida, Galíndez-Agirregoikoa Eva, García-Vivar María Luz, Gualillo Oreste, Quevedo-Abeledo Juan Carlos, Castañeda Santos, Ferraz-Amaro Iván, González-Gay Miguel Á, Genre Fernanda

机构信息

Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, IDIVAL, Hospital Universitario Marqués de Valdecilla, Avenida Cardenal Herrera Oria s/n, Lab. 201/202, 39011, Santander, Spain.

Rheumatology Division, Hospital Comarcal de Laredo, Laredo, Spain.

出版信息

Arthritis Res Ther. 2021 Apr 13;23(1):111. doi: 10.1186/s13075-021-02499-7.

DOI:
10.1186/s13075-021-02499-7
PMID:33849644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8042971/
Abstract

BACKGROUND

Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA.

METHODS

This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1.

RESULTS

Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level.

CONCLUSIONS

Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.

摘要

背景

内脏脂肪素是一种新型抗炎脂肪因子,与心血管(CV)疾病以及不同于中轴型脊柱关节炎(axSpA)的慢性炎症状态下的炎症相关。鉴于axSpA患者心血管疾病的高发病率(主要由于动脉粥样硬化加速),我们想知道内脏脂肪素是否也是这一过程中的关键分子。然而,关于内脏脂肪素在axSpA背景下对动脉粥样硬化疾病作用的数据很少。因此,我们旨在从基因和血清学水平评估内脏脂肪素在axSpA亚临床动脉粥样硬化和心血管风险中的影响。

方法

本研究纳入了510例诊断为axSpA的患者。进行颈动脉超声(US)检查以评估亚临床动脉粥样硬化的存在。通过TaqMan探针检测三种内脏脂肪素基因变异(rs2236242、rs7159023和rs35262691)的基因型。采用酶联免疫吸附测定法评估血清内脏脂肪素水平。使用STATA® v.11.1进行统计分析。

结果

女性患者的血清内脏脂肪素水平显著高于男性,与体重正常者相比,肥胖患者的血清内脏脂肪素水平也更高(p < 0.05)。在基因水平上,我们发现rs2236242的次要等位基因(A)与axSpA患者较低的血清内脏脂肪素水平相关,而rs7159023的次要等位基因(A)与较高的血清水平相关(p < 0.05)。当将评估的三种多态性组合成单倍型时,我们发现与高血清内脏脂肪素水平相关的TGC单倍型(p = 0.01)。然而,在基因和血清学水平上,均未观察到内脏脂肪素与亚临床动脉粥样硬化标志物之间存在统计学显著关联。

结论

我们的结果表明,内脏脂肪素与可能影响axSpA动脉粥样硬化进程的心血管危险因素相关。此外,我们发现一大批axSpA患者的血清内脏脂肪素浓度受基因调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cdc/8042971/297d85a88d39/13075_2021_2499_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cdc/8042971/f967abbd9ab1/13075_2021_2499_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cdc/8042971/297d85a88d39/13075_2021_2499_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cdc/8042971/f967abbd9ab1/13075_2021_2499_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cdc/8042971/297d85a88d39/13075_2021_2499_Fig2_HTML.jpg

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本文引用的文献

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The Adipokine Network in Rheumatic Joint Diseases.风湿性关节疾病中的脂肪因子网络。
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Association of circulating calprotectin with lipid profile in axial spondyloarthritis.循环钙卫蛋白与轴性脊柱关节炎脂谱的相关性。
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Molecular Mechanisms of Vaspin Action - From Adipose Tissue to Skin and Bone, from Blood Vessels to the Brain.囊泡抑素作用的分子机制——从脂肪组织到皮肤和骨骼,从血管到大脑。
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